---
title: Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
nct_id: NCT03959085
overall_status: RECRUITING
phase: PHASE3
sponsor: "Children's Oncology Group"
study_type: INTERVENTIONAL
primary_condition: B Acute Lymphoblastic Leukemia
countries: United States, Australia, Canada, New Zealand, Puerto Rico
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT03959085.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT03959085"
ct_last_update_post_date: 2026-05-05
last_seen_at: "2026-05-12T06:46:18.585Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

**Official Title:** A Phase 3 Randomized Trial of Inotuzumab Ozogamicin (IND#:133494, NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy

**NCT ID:** [NCT03959085](https://clinicaltrials.gov/study/NCT03959085)

## Key Facts

- **Status:** RECRUITING
- **Phase:** PHASE3
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 5951
- **Lead Sponsor:** Children's Oncology Group
- **Collaborators:** National Cancer Institute (NCI)
- **Conditions:** B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia
- **Start Date:** 2019-10-31
- **Completion Date:** 2032-03-31
- **CT.gov Last Update:** 2026-05-05

## Brief Summary

This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy and immunotherapy (chemo-immunotherapy) for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. Inotuzumab ozogamicin is a monoclonal antibody, which is a type of protein that can bind to certain targets on the surface of cells. Inotuzumab ozogamicin is a monoclonal antibody that is linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells by binding to the CD22 protein on the surface of the cancer cell and delivering calicheamicin inside the cells to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Blinatumomab is a specialized type of monoclonal antibody known as a bispecific T-cell engager (BiTE). It works by simultaneously binding to CD19 on cancer cells and CD3 on normal immune cells, bringing them together to destroy leukemia cells. Blinatumomab is a standard part of chemo-immunotherapy treatment for B-ALL. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin or blinatumomab.

The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemo-immunotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first phase of therapy: Induction. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-induction treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (consolidation, blinatumomab block 1, interim maintenance 1, blinatumomab block 2, delayed intensification, interim maintenance 2, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of consolidation or part of delayed intensification. Other aims of this study include evaluating 1) side effects of treatment using patient-reported outcomes and health-related quality of life, 2) the best ways to help patients adhere to oral chemotherapy regimens, 3) the relationship between levels of inotuzumab ozogamicin in the blood and side effects, 4) the impact of chemo-immunotherapy on the immune system and risk of infection, and 5) the impact of social determinants of health on outcomes. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.

## Detailed Description

PRIMARY OBJECTIVE:

I. To compare in a randomized manner the post-induction 5-year event-free survival (EFS) for children and young adults with High Risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) treated with a modified Berlin-Frankfurt-Münster (mBFM) chemo-immunotherapy backbone that includes blinatumomab and replaces Consolidation Part 2 and Delayed Intensification (DI) Part 2 with two blocks of inotuzumab ozogamicin, versus those treated with a full mBFM chemo-immunotherapy backbone that includes blinatumomab and retains Consolidation Part 2 and DI Part 2 without the addition of inotuzumab ozogamicin.

SECONDARY OBJECTIVES:

I. To describe the 5-year disease-free survival (DFS) for a favorable risk subset of National Cancer Institute (NCI) HR B-ALL (HR-Fav) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD-MTX) interim maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex. (Pre-Amendment #7B) II. To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL, including toxicity experienced during phases of therapy subsequent to inotuzumab ozogamicin.

III. To describe the 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi intravenous (IV) methotrexate without leucovorin rescue plus pegaspargase or calaspargase pegol (C-MTX).

IV. To describe the 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX.

V. To compare health-related quality of life (HRQoL) for randomized HR B-ALL patients by study arm at two defined time points: Consolidation Part 2 Day 43 (Arm D)/inotuzumab ozogamicin Block 1 Day 15 (Arm E) and day 1 of IM2 (Arms D and E).

VI. To compare symptomatic adverse events (AEs) for patients with HR B-ALL by study arm using Patient Reported Outcome (PRO) Measures.

EXPLORATORY OBJECTIVES:

I. To describe the 5-year overall survival (OS) and cumulative incidence of relapse (CIR) for randomized patients with HR B-ALL.

II. To describe the therapy administered, disease response, and survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy either during Induction, at end of induction (EOI), or at end of consolidation (EOC).

III. To define the prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow minimal residual disease (MRD) at EOI in disseminated B-LLy.

IV. To determine the impact of proposed adherence-enhancing interventions on adherence to oral mercaptopurine in patients with ALL.

V. To characterize the pharmacokinetics (PK) of inotuzumab ozogamicin when administered in the setting of first remission in pediatric and young adult patients with HR B-ALL.

VI. To explore associations between family-reported social determinants of health and survival outcomes, toxicities, and blinatumomab patterns of delivery.

VII. To describe both the short- and long-term impact of chemo-immunotherapy on measures of immune function and infectious toxicities.

OUTLINE:

B-ALL: All patients with B-ALL receive Induction therapy:

INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1. Patients also receive vincristine intravenously (IV) on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase intramuscularly (IM) on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for central nervous system \[CNS\]3 patients). Patients \< 10 years old receive dexamethasone orally (PO) twice daily (BID) or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age.

After completion of Induction treatment, patients with HR Fav B-ALL discontinue study, and patients with HR B-ALL and CD22 positive at diagnosis are randomized to Arm D or Arm E.

ARM D

* CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO QD on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (also days 29 and 43 for CNS3 patients), vincristine IV on days 15, 22, 43, and 50, pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 15 and 43. Consolidation treatment continues for 57 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis also receive radiation therapy (RT) to the testes once daily (QD) over 12 treatment fractions. After completion of Consolidation treatment, patients with MRD ≥ 25% discontinue study treatment.
* BLINATUMOMAB (BLINA) BLOCK 1: Patients receive dexamethasone PO or IV on day 1 (and day 8 for patients with MRD ≥ 5% - \<25% at end of Consolidation \[EOC\]), blinatumomab IV continuously on days 1-28, and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. After completion of Blina Block 1 treatment, patients with MRD ≥ 0.01% discontinue study treatment.
* INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.
* BLINA BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* DELAYED INTENSIFICATION PART 1: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 4 in the absence of disease progression or unacceptable toxicity. Patients then proceed to Delayed Intensification Part 2.
* DELAYED INTENSIFICATION PART 2: Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO QD on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV on days 43 and 50, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 43. Delayed Intensification Part 1 and 2 treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.
* INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IV over 2-5 or 10-15 minutes on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IM or IV over 1-2 hours on days 2 and 22 OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 2 and 23. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
* MAINTENANCE: Patients receive vincristine IV on day 1 of each cycle, prednisone or prednisolone PO BID or IV on days 1-5 of each cycle, mercaptopurine PO QD on days 1-84 of each cycle, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and methotrexate IT on day 1 of each cycle. Patients with CNS3 at diagnosis also receive cranial RT over 10 treatment fractions QD, 5 days per week, during the first 4 weeks of Maintenance treatment. Cycles repeat every 84 days until 2 years from start of Blina Block 1 treatment in the absence of disease progression or unacceptable toxicity.

ARM E:

* CONSOLIDATION PART 1: Patients receive cyclophosphamide IV over 30-60 minutes on day 1, cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11, mercaptopurine PO QD on days 1-14, methotrexate IT on days 1, 8, 15, and 22 (NOTE: Patients with CNS3 omit days 15 and 22), vincristine IV on days 15 and 22, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 15. Treatment continues for 29 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis also receive RT to the testes QD over 12 treatment fractions.
* INOTUZUMAB OZOGAMICIN (InO) BLOCK 1: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1 (and day 15 for patients with CNS3). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. After completion of InO Block 1 treatment, patients with MRD ≥ 25% discontinue study treatment.
* BLINA BLOCK 1: Patients receive dexamethasone PO or IV on day 1 (and day 8 for patients with MRD ≥ 5% - \<25% at end of InO Block 1), blinatumomab IV continuously on days 1-28, and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. After completion of Blina Block 1 treatment, patients with MRD ≥ 0.01% discontinue study treatment.
* INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.
* BLINA BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* DELAYED INTENSIFICATION PART 1: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 4 in the absence of disease progression or unacceptable toxicity. Patients then proceed to Delayed Intensification Part 2.
* InO BLOCK 2: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
* INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IV over 2-5 or 10-15 minutes on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IM or IV over 1-2 hours on days 2 and 22 OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 2 and 23. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
* MAINTENANCE: Patients receive vincristine IV on day 1 of each cycle, prednisone or prednisolone PO BID or IV on days 1-5 of each cycle, mercaptopurine PO QD on days 1-84 of each cycle, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and methotrexate IT on day 1 of each cycle. Patients with CNS3 at diagnosis also receive cranial RT over 10 treatment fractions QD, 5 days per week, during the first 4 weeks of Maintenance treatment. Cycles repeat every 84 days for 2 years in the absence of disease progression or unacceptable toxicity.

ARM I: MPAL

* INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients \< 10 years old receive dexamethasone PO BID or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. Patients with MRD ≥ 5% at EOI discontinue study treatment.
* CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 for CNS3 patients), vincristine IV on days 15, 22, 43, and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by EOC and continued evidence of testicular disease at end of induction (EOI) undergo testicular RT over 12 once-daily fractions. Calaspargase pegol can only be given to patients less than 22 years of age. Patients with MRD ≥ 0.01% at EOC discontinue study treatment.

ARM II: B-LLY

* INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients \< 10 years old receive dexamethasone PO BID or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age.
* CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 CNS3 patients), vincristine IV on days 15, 22, 43, and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by the EOI will and continued evidence of testicular disease at EOI undergo testicular RT over 12 once-daily fractions. Calaspargase pegol can only be given to patients less than 22 years of age. Patients without complete response (CR) at EOC discontinue study treatment.

ARM I AND II: MPAL AND B-LLY (POST-CONSOLIDATION THERAPY)

* INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.
* DELAYED INTENSIFICATION (PART 1): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts 1 and 2 of Delayed Intensification) continues for 63 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age.
* DELAYED INTENSIFICATION (PART 2): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts 1 and 2 of Delayed Intensification) continues for 63 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age.
* INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 (pegaspargase) or (calaspargase) 23 or pegaspargase IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age.
* MAINTENANCE: Patients receive vincristine IV on days 1, prednisone or prednisolone PO BID or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate PO on days 8, 15, 22, 29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71, and 78, and methotrexate IT on days 1 (and 29 of cycles 1-2 for patients who do not receive cranial radiation). Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10 fractions over 4 weeks.

Patients undergo blood sample collection and bone marrow aspiration and biopsy on study. B-LLy patients undergo computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and/or bone scan on study.

After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for 2 years, every 4-6 months for the third year, then every 6-12 months for years 4-5.

## Eligibility

- **Minimum age:** 365 Days
- **Maximum age:** 25 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Inclusion Criteria:

* B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
* APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
* Patients must be \> 365 days and \< 25 years of age
* White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):

  * Age 1-9.99 years: WBC \>= 50,000/uL
  * Age 10-24.99 years: Any WBC
  * Age 1-9.99 years: WBC \< 50,000/uL with one or more of the following:

    * Testicular leukemia
    * CNS leukemia (CNS3)
    * Steroid pretreatment.
* White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):

  * Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
* Patient has newly diagnosed B-ALL or MPAL (by World Health Organization \[WHO\] 2016 criteria) with \>= 25% blasts on a bone marrow (BM) aspirate;

  * OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
  * OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
* Patient has newly diagnosed B-LLy Murphy stages III or IV.
* Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
* Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
* Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.

Exclusion Criteria:

* Patients with Down syndrome are not eligible
* With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
* Patients who have received \> 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
* Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing \> 1,000/uL circulating leukemia cells.
* Patients with acute undifferentiated leukemia (AUL) are not eligible.
* For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:

  * T-lymphoblastic lymphoma.
  * Morphologically unclassifiable lymphoma.
  * Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
* Patients with known Charcot-Marie-Tooth disease.
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
* Patients requiring radiation at diagnosis.
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males.
```

## Arms

- **Arm D (CD 22 positive HR B-ALL)** (ACTIVE_COMPARATOR) — See detailed description for Arm D
- **Arm E (CD22 positive HR B-ALL)** (EXPERIMENTAL) — See detailed description for Arm E.
- **Arm I (MPAL)** (EXPERIMENTAL) — See Detailed Description for Arm I.
- **Arm II (B-LLy)** (EXPERIMENTAL) — See Detailed Description for Arm II.

## Interventions

- **Biospecimen Collection** (PROCEDURE) — Undergo blood sample collection
- **Blinatumomab** (BIOLOGICAL) — Given IV
- **Bone Marrow Aspiration** (PROCEDURE) — Undergo bone marrow aspiration
- **Bone Marrow Biopsy** (PROCEDURE) — Undergo bone marrow biopsy
- **Bone Scan** (PROCEDURE) — Undergo bone scan
- **Calaspargase Pegol** (DRUG) — Given IV
- **Computed Tomography** (PROCEDURE) — Undergo CT
- **Cyclophosphamide** (DRUG) — Given IV
- **Cytarabine** (DRUG) — Given IV, IT, or SC
- **Daunorubicin Hydrochloride** (DRUG) — Given IV
- **Dexamethasone** (DRUG) — Given PO or IV
- **Doxorubicin Hydrochloride** (DRUG) — Given IV
- **Inotuzumab Ozogamicin** (BIOLOGICAL) — Given IV
- **Leucovorin Calcium** (DRUG) — Given PO or IV
- **Magnetic Resonance Imaging** (PROCEDURE) — Undergo MRI
- **Mercaptopurine** (DRUG) — Given PO
- **Methotrexate** (DRUG) — Given IT or IV
- **Pegaspargase** (DRUG) — Given IV or IM
- **Positron Emission Tomography** (PROCEDURE) — Undergo PET
- **Prednisolone** (DRUG) — Given PO or IV
- **Prednisone** (DRUG) — Given PO or IV
- **Questionnaire Administration** (OTHER) — Ancillary studies
- **Radiation Therapy** (RADIATION) — Undergo testicular radiation therapy
- **Radiation Therapy** (RADIATION) — Undergo cranial radiation therapy
- **Thioguanine** (DRUG) — Given PO
- **Vincristine Sulfate** (DRUG) — Given IV

## Primary Outcomes

- **Post-induction 5-year event-free survival (EFS)** _(time frame: From study entry to first event (induction failure, induction death, end of induction [EOI] minimal residual disease [MRD] ≥ 5%,EO consolidation [C] MRD ≥ 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years)_ — Will compare in a randomized manner the post-induction 5-year EFS for children and young adults with High Risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) treated with a modified Berlin-Frankfurt-Münster (mBFM) chemo-immunotherapy backbone that includes blinatumomab and replaces Consolidation Part 2 and Delayed Intensification (DI) Part 2 with two blocks of inotuzumab ozogamicin, versus those treated with a full mBFM chemo-immunotherapy backbone that includes blinatumomab and retains Consolidation Part 2 and DI Part 2 without the addition of inotuzumab ozogamicin.

## Secondary Outcomes

- **5-year DFS for favorable risk subset of NCI HR B-ALL (HR favorable) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex** _(time frame: From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years)_
- **Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL** _(time frame: Up to 5 years)_
- **5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi escalating intravenous MTX without leucovorin rescue+pegaspargase or calaspargase pegol** _(time frame: From study entry to first event (induction failure, Induction death, end of induction (EOI) minimal residual disease (MRD) >= 5%, EOC MRD >= 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years)_
- **5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX** _(time frame: From study entry to first event (progressive disease, induction death, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years)_
- **Health-related quality of life (HRQoL) for HR B-ALL** _(time frame: Consolidation Part 2 Day 43 (Arm D)/Inotuzumab ozogamicin Block 1 Day 15 (Arm E) up to Day 1 of IM2 (Arms D and E))_
- **Incidence of symptomatic AEs for patients with HR B-ALL** _(time frame: Up to 5 years)_

## Locations (230)

- Children's Hospital of Alabama, Birmingham, Alabama, United States — _RECRUITING_
- USA Health Strada Patient Care Center, Mobile, Alabama, United States — _RECRUITING_
- Providence Alaska Medical Center, Anchorage, Alaska, United States — _RECRUITING_
- Banner Children's at Desert, Mesa, Arizona, United States — _RECRUITING_
- Phoenix Childrens Hospital, Phoenix, Arizona, United States — _RECRUITING_
- Banner University Medical Center - Tucson, Tucson, Arizona, United States — _RECRUITING_
- Arkansas Children's Hospital, Little Rock, Arkansas, United States — _RECRUITING_
- Kaiser Permanente Downey Medical Center, Downey, California, United States — _RECRUITING_
- City of Hope Comprehensive Cancer Center, Duarte, California, United States — _RECRUITING_
- Loma Linda University Medical Center, Loma Linda, California, United States — _RECRUITING_
- Miller Children's and Women's Hospital Long Beach, Long Beach, California, United States — _RECRUITING_
- Children's Hospital Los Angeles, Los Angeles, California, United States — _RECRUITING_
- Cedars-Sinai Medical Center, Los Angeles, California, United States — _RECRUITING_
- Mattel Children's Hospital UCLA, Los Angeles, California, United States — _SUSPENDED_
- Valley Children's Hospital, Madera, California, United States — _RECRUITING_
- UCSF Benioff Children's Hospital Oakland, Oakland, California, United States — _RECRUITING_
- Kaiser Permanente-Oakland, Oakland, California, United States — _RECRUITING_
- Children's Hospital of Orange County, Orange, California, United States — _RECRUITING_
- Lucile Packard Children's Hospital Stanford University, Palo Alto, California, United States — _RECRUITING_
- Sutter Medical Center Sacramento, Sacramento, California, United States — _RECRUITING_
- University of California Davis Comprehensive Cancer Center, Sacramento, California, United States — _RECRUITING_
- Rady Children's Hospital - San Diego, San Diego, California, United States — _RECRUITING_
- Naval Medical Center -San Diego, San Diego, California, United States — _RECRUITING_
- UCSF Medical Center-Mission Bay, San Francisco, California, United States — _RECRUITING_
- Santa Barbara Cottage Hospital, Santa Barbara, California, United States — _RECRUITING_
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States — _ACTIVE_NOT_RECRUITING_
- Children's Hospital Colorado, Aurora, Colorado, United States — _RECRUITING_
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center, Denver, Colorado, United States — _RECRUITING_
- Connecticut Children's Medical Center, Hartford, Connecticut, United States — _RECRUITING_
- Yale University, New Haven, Connecticut, United States — _RECRUITING_
- Alfred I duPont Hospital for Children, Wilmington, Delaware, United States — _RECRUITING_
- MedStar Georgetown University Hospital, Washington D.C., District of Columbia, United States — _SUSPENDED_
- Children's National Medical Center, Washington D.C., District of Columbia, United States — _RECRUITING_
- Broward Health Medical Center, Fort Lauderdale, Florida, United States — _RECRUITING_
- Golisano Children's Hospital of Southwest Florida, Fort Myers, Florida, United States — _RECRUITING_
- UF Health Cancer Institute - Gainesville, Gainesville, Florida, United States — _RECRUITING_
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood, Florida, United States — _RECRUITING_
- Nemours Children's Clinic-Jacksonville, Jacksonville, Florida, United States — _RECRUITING_
- Palms West Radiation Therapy, Loxahatchee Groves, Florida, United States — _ACTIVE_NOT_RECRUITING_
- University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States — _RECRUITING_
- Nicklaus Children's Hospital, Miami, Florida, United States — _RECRUITING_
- Miami Cancer Institute, Miami, Florida, United States — _ACTIVE_NOT_RECRUITING_
- AdventHealth Orlando, Orlando, Florida, United States — _RECRUITING_
- Arnold Palmer Hospital for Children, Orlando, Florida, United States — _RECRUITING_
- Nemours Children's Hospital, Orlando, Florida, United States — _RECRUITING_
- Nemours Children's Clinic - Pensacola, Pensacola, Florida, United States — _RECRUITING_
- Sacred Heart Hospital, Pensacola, Florida, United States — _SUSPENDED_
- Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States — _RECRUITING_
- Tampa General Hospital, Tampa, Florida, United States — _RECRUITING_
- Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa, Florida, United States — _RECRUITING_
- Saint Mary's Medical Center, West Palm Beach, Florida, United States — _RECRUITING_
- Children's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta, Georgia, United States — _RECRUITING_
- Augusta University Medical Center, Augusta, Georgia, United States — _RECRUITING_
- Atrium Health Navicent, Macon, Georgia, United States — _RECRUITING_
- Memorial Health University Medical Center, Savannah, Georgia, United States — _RECRUITING_
- Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, United States — _RECRUITING_
- Saint Luke's Cancer Institute - Boise, Boise, Idaho, United States — _RECRUITING_
- Lurie Children's Hospital-Chicago, Chicago, Illinois, United States — _RECRUITING_
- University of Illinois, Chicago, Illinois, United States — _RECRUITING_
- University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States — _RECRUITING_
- Loyola University Medical Center, Maywood, Illinois, United States — _RECRUITING_
- Advocate Children's Hospital-Oak Lawn, Oak Lawn, Illinois, United States — _RECRUITING_
- Advocate Children's Hospital-Park Ridge, Park Ridge, Illinois, United States — _RECRUITING_
- Saint Jude Midwest Affiliate, Peoria, Illinois, United States — _RECRUITING_
- Southern Illinois University School of Medicine, Springfield, Illinois, United States — _SUSPENDED_
- Northwestern Medicine Central DuPage Hospital, Winfield, Illinois, United States — _RECRUITING_
- Riley Hospital for Children, Indianapolis, Indiana, United States — _RECRUITING_
- Ascension Saint Vincent Indianapolis Hospital, Indianapolis, Indiana, United States — _RECRUITING_
- Blank Children's Hospital, Des Moines, Iowa, United States — _RECRUITING_
- University of Iowa/Holden Comprehensive Cancer Center, Iowa City, Iowa, United States — _RECRUITING_
- Wesley Medical Center, Wichita, Kansas, United States — _RECRUITING_
- University of Kentucky/Markey Cancer Center, Lexington, Kentucky, United States — _RECRUITING_
- Norton Children's Hospital, Louisville, Kentucky, United States — _RECRUITING_
- Children's Hospital New Orleans, New Orleans, Louisiana, United States — _RECRUITING_
- Ochsner Medical Center Jefferson, New Orleans, Louisiana, United States — _RECRUITING_
- Eastern Maine Medical Center, Bangor, Maine, United States — _RECRUITING_
- Maine Children's Cancer Program, Scarborough, Maine, United States — _RECRUITING_
- University of Maryland/Greenebaum Cancer Center, Baltimore, Maryland, United States — _RECRUITING_
- Sinai Hospital of Baltimore, Baltimore, Maryland, United States — _RECRUITING_
- Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, United States — _RECRUITING_
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States — _RECRUITING_
- Tufts Children's Hospital, Boston, Massachusetts, United States — _ACTIVE_NOT_RECRUITING_
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States — _RECRUITING_
- Dana-Farber Cancer Institute, Boston, Massachusetts, United States — _RECRUITING_
- Baystate Medical Center, Springfield, Massachusetts, United States — _RECRUITING_
- UMass Memorial Medical Center - University Campus, Worcester, Massachusetts, United States — _RECRUITING_
- C S Mott Children's Hospital, Ann Arbor, Michigan, United States — _RECRUITING_
- Children's Hospital of Michigan, Detroit, Michigan, United States — _RECRUITING_
- Henry Ford Health Saint John Hospital, Detroit, Michigan, United States — _ACTIVE_NOT_RECRUITING_
- Michigan State University, East Lansing, Michigan, United States — _ACTIVE_NOT_RECRUITING_
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids, Michigan, United States — _RECRUITING_
- Bronson Methodist Hospital, Kalamazoo, Michigan, United States — _RECRUITING_
- Corewell Health Children's, Royal Oak, Michigan, United States — _RECRUITING_
- Children's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota, United States — _RECRUITING_
- University of Minnesota/Masonic Cancer Center, Minneapolis, Minnesota, United States — _RECRUITING_
- Mayo Clinic in Rochester, Rochester, Minnesota, United States — _RECRUITING_
- University of Mississippi Medical Center, Jackson, Mississippi, United States — _RECRUITING_
- University of Missouri Children's Hospital, Columbia, Missouri, United States — _RECRUITING_
- Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States — _RECRUITING_
- Cardinal Glennon Children's Medical Center, St Louis, Missouri, United States — _RECRUITING_
- Washington University School of Medicine, St Louis, Missouri, United States — _RECRUITING_
- Mercy Hospital Saint Louis, St Louis, Missouri, United States — _RECRUITING_
- Children's Hospital and Medical Center of Omaha, Omaha, Nebraska, United States — _RECRUITING_
- University of Nebraska Medical Center, Omaha, Nebraska, United States — _RECRUITING_
- University Medical Center of Southern Nevada, Las Vegas, Nevada, United States — _SUSPENDED_
- Sunrise Hospital and Medical Center, Las Vegas, Nevada, United States — _SUSPENDED_
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas, Nevada, United States — _RECRUITING_
- Summerlin Hospital Medical Center, Las Vegas, Nevada, United States — _RECRUITING_
- Renown Regional Medical Center, Reno, Nevada, United States — _RECRUITING_
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon, New Hampshire, United States — _RECRUITING_
- Hackensack University Medical Center, Hackensack, New Jersey, United States — _RECRUITING_
- Morristown Medical Center, Morristown, New Jersey, United States — _RECRUITING_
- Jersey Shore Medical Center, Neptune City, New Jersey, United States — _RECRUITING_
- Saint Peter's University Hospital, New Brunswick, New Jersey, United States — _RECRUITING_
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States — _RECRUITING_
- Newark Beth Israel Medical Center, Newark, New Jersey, United States — _RECRUITING_
- Saint Joseph's Regional Medical Center, Paterson, New Jersey, United States — _RECRUITING_
- Presbyterian Hospital, Albuquerque, New Mexico, United States — _RECRUITING_
- University of New Mexico Cancer Center, Albuquerque, New Mexico, United States — _RECRUITING_
- Albany Medical Center, Albany, New York, United States — _RECRUITING_
- Maimonides Medical Center, Brooklyn, New York, United States — _RECRUITING_
- Roswell Park Cancer Institute, Buffalo, New York, United States — _RECRUITING_
- NYU Langone Hospital - Long Island, Mineola, New York, United States — _RECRUITING_
- The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, New York, United States — _RECRUITING_
- Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, New York, United States — _RECRUITING_
- Mount Sinai Hospital, New York, New York, United States — _RECRUITING_
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, New York, United States — _RECRUITING_
- Memorial Sloan Kettering Cancer Center, New York, New York, United States — _RECRUITING_
- NYP/Weill Cornell Medical Center, New York, New York, United States — _RECRUITING_
- University of Rochester, Rochester, New York, United States — _RECRUITING_
- Stony Brook University Medical Center, Stony Brook, New York, United States — _RECRUITING_
- State University of New York Upstate Medical University, Syracuse, New York, United States — _RECRUITING_
- Montefiore Medical Center - Moses Campus, The Bronx, New York, United States — _RECRUITING_
- New York Medical College, Valhalla, New York, United States — _RECRUITING_
- Mission Hospital, Asheville, North Carolina, United States — _RECRUITING_
- UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States — _RECRUITING_
- Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina, United States — _RECRUITING_
- Novant Health Presbyterian Medical Center, Charlotte, North Carolina, United States — _RECRUITING_
- Duke University Medical Center, Durham, North Carolina, United States — _RECRUITING_
- East Carolina University, Greenville, North Carolina, United States — _RECRUITING_
- Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States — _RECRUITING_
- Sanford Broadway Medical Center, Fargo, North Dakota, United States — _RECRUITING_
- Children's Hospital Medical Center of Akron, Akron, Ohio, United States — _RECRUITING_
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States — _RECRUITING_
- Rainbow Babies and Childrens Hospital, Cleveland, Ohio, United States — _RECRUITING_
- Cleveland Clinic Foundation, Cleveland, Ohio, United States — _RECRUITING_
- Nationwide Children's Hospital, Columbus, Ohio, United States — _RECRUITING_
- Dayton Children's Hospital, Dayton, Ohio, United States — _RECRUITING_
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo, Ohio, United States — _RECRUITING_
- University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States — _RECRUITING_
- Natalie Warren Bryant Cancer Center at Saint Francis, Tulsa, Oklahoma, United States — _RECRUITING_
- Legacy Emanuel Children's Hospital, Portland, Oregon, United States — _RECRUITING_
- Oregon Health and Science University, Portland, Oregon, United States — _RECRUITING_
- Lehigh Valley Hospital-Cedar Crest, Allentown, Pennsylvania, United States — _RECRUITING_
- Geisinger Medical Center, Danville, Pennsylvania, United States — _RECRUITING_
- Penn State Children's Hospital, Hershey, Pennsylvania, United States — _RECRUITING_
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States — _RECRUITING_
- Saint Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States — _RECRUITING_
- Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States — _RECRUITING_
- Rhode Island Hospital, Providence, Rhode Island, United States — _RECRUITING_
- Medical University of South Carolina, Charleston, South Carolina, United States — _RECRUITING_
- Prisma Health Richland Hospital, Columbia, South Carolina, United States — _RECRUITING_
- BI-LO Charities Children's Cancer Center, Greenville, South Carolina, United States — _RECRUITING_
- Sanford USD Medical Center - Sioux Falls, Sioux Falls, South Dakota, United States — _RECRUITING_
- T C Thompson Children's Hospital, Chattanooga, Tennessee, United States — _RECRUITING_
- East Tennessee Childrens Hospital, Knoxville, Tennessee, United States — _RECRUITING_
- The Children's Hospital at TriStar Centennial, Nashville, Tennessee, United States — _RECRUITING_
- Vanderbilt University/Ingram Cancer Center, Nashville, Tennessee, United States — _RECRUITING_
- Texas Tech University Health Sciences Center-Amarillo, Amarillo, Texas, United States — _RECRUITING_
- Dell Children's Medical Center of Central Texas, Austin, Texas, United States — _RECRUITING_
- Driscoll Children's Hospital, Corpus Christi, Texas, United States — _RECRUITING_
- Medical City Dallas Hospital, Dallas, Texas, United States — _RECRUITING_
- UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas, United States — _RECRUITING_
- El Paso Children's Hospital, El Paso, Texas, United States — _RECRUITING_
- Cook Children's Medical Center, Fort Worth, Texas, United States — _RECRUITING_
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston, Texas, United States — _RECRUITING_
- M D Anderson Cancer Center, Houston, Texas, United States — _RECRUITING_
- Covenant Children's Hospital, Lubbock, Texas, United States — _RECRUITING_
- UMC Cancer Center / UMC Health System, Lubbock, Texas, United States — _RECRUITING_
- Vannie Cook Children's Clinic, McAllen, Texas, United States — _RECRUITING_
- Children's Hospital of San Antonio, San Antonio, Texas, United States — _RECRUITING_
- Methodist Children's Hospital of South Texas, San Antonio, Texas, United States — _RECRUITING_
- University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States — _RECRUITING_
- Scott and White Memorial Hospital, Temple, Texas, United States — _RECRUITING_
- Primary Children's Hospital, Salt Lake City, Utah, United States — _RECRUITING_
- University of Vermont and State Agricultural College, Burlington, Vermont, United States — _RECRUITING_
- University of Virginia Cancer Center, Charlottesville, Virginia, United States — _RECRUITING_
- Inova Fairfax Hospital, Falls Church, Virginia, United States — _RECRUITING_
- Children's Hospital of The King's Daughters, Norfolk, Virginia, United States — _RECRUITING_
- Naval Medical Center - Portsmouth, Portsmouth, Virginia, United States — _RECRUITING_
- VCU Massey Comprehensive Cancer Center, Richmond, Virginia, United States — _RECRUITING_
- Carilion Children's, Roanoke, Virginia, United States — _RECRUITING_
- Seattle Children's Hospital, Seattle, Washington, United States — _RECRUITING_
- Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington, United States — _RECRUITING_
- Mary Bridge Children's Hospital and Health Center, Tacoma, Washington, United States — _RECRUITING_
- Madigan Army Medical Center, Tacoma, Washington, United States — _SUSPENDED_
- West Virginia University Charleston Division, Charleston, West Virginia, United States — _RECRUITING_
- Edwards Comprehensive Cancer Center, Huntington, West Virginia, United States — _SUSPENDED_
- West Virginia University Healthcare, Morgantown, West Virginia, United States — _SUSPENDED_
- Saint Vincent Hospital Cancer Center Green Bay, Green Bay, Wisconsin, United States — _RECRUITING_
- _and 30 more_

## Recent Field Changes (last 30 days)

- `locations.john hunter children's hospital|hunter regional mail centre|new south wales|australia` — added _(2026-05-12)_
- `locations.the children's hospital at westmead|westmead|new south wales|australia` — added _(2026-05-12)_
- `locations.queensland children's hospital|south brisbane|queensland|australia` — added _(2026-05-12)_
- `locations.women's and children's hospital-adelaide|north adelaide|south australia|australia` — added _(2026-05-12)_
- `locations.monash medical center-clayton campus|clayton|victoria|australia` — added _(2026-05-12)_
- `locations.royal children's hospital|parkville|victoria|australia` — added _(2026-05-12)_
- `locations.perth children's hospital|perth|western australia|australia` — added _(2026-05-12)_
- `locations.alberta children's hospital|calgary|alberta|canada` — added _(2026-05-12)_
- `locations.university of alberta hospital|edmonton|alberta|canada` — added _(2026-05-12)_
- `locations.british columbia children's hospital|vancouver|british columbia|canada` — added _(2026-05-12)_
- `locations.cancercare manitoba|winnipeg|manitoba|canada` — added _(2026-05-12)_
- `locations.janeway child health centre|st. john's|newfoundland and labrador|canada` — added _(2026-05-12)_
- `locations.iwk health centre|halifax|nova scotia|canada` — added _(2026-05-12)_
- `locations.mcmaster children's hospital at hamilton health sciences|hamilton|ontario|canada` — added _(2026-05-12)_
- `locations.kingston health sciences centre|kingston|ontario|canada` — added _(2026-05-12)_
- `locations.children's hospital|london|ontario|canada` — added _(2026-05-12)_
- `locations.children's hospital of eastern ontario|ottawa|ontario|canada` — added _(2026-05-12)_
- `locations.hospital for sick children|toronto|ontario|canada` — added _(2026-05-12)_
- `locations.the montreal children's hospital of the muhc|montreal|quebec|canada` — added _(2026-05-12)_
- `locations.centre hospitalier universitaire de sherbrooke-fleurimont|sherbrooke|quebec|canada` — added _(2026-05-12)_
- `locations.jim pattison children's hospital|saskatoon|saskatchewan|canada` — added _(2026-05-12)_
- `locations.saskatoon cancer centre|saskatoon|saskatchewan|canada` — added _(2026-05-12)_
- `locations.chu de quebec-centre hospitalier de l'universite laval (chul)|québec||canada` — added _(2026-05-12)_
- `locations.starship children's hospital|grafton|auckland|new zealand` — added _(2026-05-12)_
- `locations.christchurch hospital|christchurch||new zealand` — added _(2026-05-12)_
- `locations.hima san pablo oncologic hospital|caguas||puerto rico` — added _(2026-05-12)_
- `locations.university pediatric hospital|san juan||puerto rico` — added _(2026-05-12)_
- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `sponsor.collaborators` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.children's hospital of alabama|birmingham|alabama|united states` — added _(2026-05-12)_
- `locations.usa health strada patient care center|mobile|alabama|united states` — added _(2026-05-12)_
- `locations.providence alaska medical center|anchorage|alaska|united states` — added _(2026-05-12)_
- `locations.banner children's at desert|mesa|arizona|united states` — added _(2026-05-12)_
- `locations.phoenix childrens hospital|phoenix|arizona|united states` — added _(2026-05-12)_
- `locations.banner university medical center - tucson|tucson|arizona|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT03959085.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT03959085*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*