--- title: Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma nct_id: NCT03023878 overall_status: COMPLETED phase: PHASE2 sponsor: Amgen study_type: INTERVENTIONAL primary_condition: High-risk Diffuse Large B-Cell Lymphoma countries: United States, Canada, France, Germany, Spain, United Kingdom canonical_url: "https://parkinsonspathways.com/agent/trials/NCT03023878.md" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT03023878" ct_last_update_post_date: 2020-09-14 last_seen_at: "2026-05-12T07:33:43.996Z" source: ClinicalTrials.gov (mirrored, no enrichment) --- # Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma **Official Title:** 20150288 A Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL) **NCT ID:** [NCT03023878](https://clinicaltrials.gov/study/NCT03023878) ## Key Facts - **Status:** COMPLETED - **Phase:** PHASE2 - **Study Type:** INTERVENTIONAL - **Target Enrollment:** 47 - **Lead Sponsor:** Amgen - **Conditions:** High-risk Diffuse Large B-Cell Lymphoma - **Start Date:** 2017-03-13 - **Completion Date:** 2019-10-28 - **CT.gov Last Update:** 2020-09-14 ## Brief Summary A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL. ## Detailed Description The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab. ## Eligibility - **Minimum age:** 18 Years - **Maximum age:** 100 Years - **Sex:** ALL - **Healthy Volunteers:** No ``` Inclusion criteria: * Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Age ≥ 18 at time of informed consent * Subject must have untreated histologically proven high-risk DLBCL defined by atleast one of the following: * International Prognostic Index (IPI) for Diffuse Large B-cell Lymphoma 3 to 5 (representing high intermedidate - high ratings), * Double-hit or higher or double protein expression * Eastern Cooperative Oncology Group performance status ≤ 2. * Subject meets the criteria per investigator's institution to receive standard of care (SOC) rituximab-chemotherapy (ie, R-CHOP \[14 or 21\] or R-DA-EPOCH or R-CHOEP) of 6 cycles. Subjects may be enrolled on study prior to cycle 1 or cycle 2 of SOC R-chemotherapy * Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as: * Hematological: Absolute neutrophil count ≥1\*10\^9/L; Platelet count ≥75\*10\^9/L;Hemoglobin ≥8g/dL * Renal: Creatinine clearance ≥50mL/min; * Hepatic: Aspartate aminotransferase/Alanine aminotransferase \<3\*upper limit of normal (ULN); Total bilirubin \<2\*ULN (unless Gilbert's Disease or if liver involvement with lymphoma) * Subject must have completed 6 cycles of SOC R-chemotherapy and achieved CR, PR or stable disease by PET/CT performed 3 weeks (± 3 days) after cycle 6 of SOC R-chemotherapy. Subjects with progressive disease (PD) are not eligible for treatment with blinatumomab and will end the study. Exclusion Criteria: * Clinically relevant central nervous system (CNS) pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis * Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab * Current autoimmune disease or history of autoimmune disease with potential of CNS involvement * Subject has active infection requiring systemic therapy * Prior anti-CD19 therapies * Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus * History of other malignancy within the past 3 years with the following exceptions: * Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician * Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease * Adequately treated cervical carcinoma in situ without evidence of disease * Adequately treated breast ductal carcinoma in situ without evidence of disease * Prostatic intraepithelial neoplasia without evidence of prostate cancer * Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ * Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing. * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge. * History/evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab. * Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded. ``` ## Arms - **Blinatumomab** (EXPERIMENTAL) — Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time. An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days. There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death. ## Interventions - **Blinatumomab** (DRUG) — Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion. - **Investigator's Choice Chemotherapy** (DRUG) — During the run-in period participants received 6 cycles of standard of care rituximab-chemotherapy dosed per investigator's institution standard as follows: * R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,prednisone) * R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or * R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide). - **Dexamethasone** (DRUG) — Dexamethasone 20 mg IV: within 1 hour prior to start of treatment in each treatment cycle, and within 1 hour prior to dose-step (increase). ## Primary Outcomes - **Participants With Treatment-Emergent (Blinatumomab) Adverse Events** _(time frame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days)_ — Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death. - **Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment** _(time frame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days)_ — Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death. ## Secondary Outcomes - **Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period** _(time frame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2)_ - **Kaplan-Meier Estimates for Duration of Response** _(time frame: The median (range) follow-up time was 11.5 (8.2, 14.5) months)_ - **Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period** _(time frame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2)_ - **Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab** _(time frame: The median (range) follow-up time was 12.0 (10.7, 14.5) months.)_ - **Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab** _(time frame: The median (range) follow-up time was 12.0 (8.2, 14.5))_ - **Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)** _(time frame: Day 1 up to 14.5 months)_ - **Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1** _(time frame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle)_ - **Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1** _(time frame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle)_ ## Locations (24) - Research Site, Chicago, Illinois, United States - Research Site, Maywood, Illinois, United States - Research Site, New Orleans, Louisiana, United States - Research Site, Baltimore, Maryland, United States - Research Site, New Brunswick, New Jersey, United States - Research Site, Oklahoma City, Oklahoma, United States - Research Site, Portland, Oregon, United States - Research Site, Greenville, South Carolina, United States - Research Site, Edmonton, Alberta, Canada - Research Site, Sault Ste. Marie, Ontario, Canada - Research Site, Toronto, Ontario, Canada - Research Site, Créteil, France - Research Site, Paris, France - Research Site, Dresden, Germany - Research Site, Ulm, Germany - Research Site, Seville, Andalusia, Spain - Research Site, Salamanca, Castille and León, Spain - Research Site, Barcelona, Catalonia, Spain - Research Site, L'Hospitalet de Llobregat, Catalonia, Spain - Research Site, A Coruña, Galicia, Spain - Research Site, Valencia, Valencia, Spain - Research Site, Madrid, Spain - Research Site, Bristol, United Kingdom - Research Site, Sheffield, United Kingdom ## Recent Field Changes (last 30 days) - `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)_ - `locations.research site|dresden||germany` — added _(2026-05-12)_ - `armsInterventions.interventions` — added _(2026-05-12)_ - `sponsor.lead` — added _(2026-05-12)_ - `results.hasResults` — added _(2026-05-12)_ - `locations.research site|chicago|illinois|united states` — added _(2026-05-12)_ - `locations.research site|maywood|illinois|united states` — added _(2026-05-12)_ - `locations.research site|new orleans|louisiana|united states` — added _(2026-05-12)_ - `locations.research site|baltimore|maryland|united states` — added _(2026-05-12)_ - `locations.research site|new brunswick|new jersey|united states` — added _(2026-05-12)_ - `locations.research site|oklahoma city|oklahoma|united states` — added _(2026-05-12)_ - `locations.research site|portland|oregon|united states` — added _(2026-05-12)_ - `locations.research site|greenville|south carolina|united states` — added _(2026-05-12)_ - `locations.research site|edmonton|alberta|canada` — added _(2026-05-12)_ - `locations.research site|sault ste. marie|ontario|canada` — added _(2026-05-12)_ - `locations.research site|toronto|ontario|canada` — added _(2026-05-12)_ - `locations.research site|créteil||france` — added _(2026-05-12)_ - `locations.research site|paris||france` — added _(2026-05-12)_ - `locations.research site|ulm||germany` — added _(2026-05-12)_ - `locations.research site|seville|andalusia|spain` — added _(2026-05-12)_ - `locations.research site|salamanca|castille and león|spain` — added _(2026-05-12)_ - `locations.research site|barcelona|catalonia|spain` — added _(2026-05-12)_ - `locations.research site|l'hospitalet de llobregat|catalonia|spain` — added _(2026-05-12)_ - `locations.research site|a coruña|galicia|spain` — added _(2026-05-12)_ - `locations.research site|valencia|valencia|spain` — added _(2026-05-12)_ - `locations.research site|madrid||spain` — added _(2026-05-12)_ - `locations.research site|bristol||united kingdom` — added _(2026-05-12)_ - `locations.research site|sheffield||united kingdom` — added _(2026-05-12)_ --- *Canonical: https://parkinsonspathways.com/agent/trials/NCT03023878.md* *Source data (authoritative): https://clinicaltrials.gov/study/NCT03023878* *This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*