Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma

NCT03023878 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 201502882016-002190-35
• Study Type: interventional
• Target: 47
• Locations: 6 countries
• Sites: 24

Brief Summary

A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.

Conditions

High-risk Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Participants With Treatment-Emergent (Blinatumomab) Adverse Events

  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.

  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

• Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment

  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.

  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

Secondary Outcomes (8)

• 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

  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

  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

  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

  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

  The median (range) follow-up time was 12.0 (8.2, 14.5)

Study Arms (1)

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.

Drug: Blinatumomab; Drug: Investigator's Choice Chemotherapy; Drug: Dexamethasone

Interventions

Blinatumomab DRUG

Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion.

Also known as: AMG103, BlinCyto

Blinatumomab

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).

Blinatumomab

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).

Also known as: corticosteroid

Blinatumomab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (24)

Research Site

Chicago, Illinois, 60612, United States

Location

Research Site

Maywood, Illinois, 60153, United States

Location

Research Site

New Orleans, Louisiana, 70112, United States

Location

Research Site

Baltimore, Maryland, 21201, United States

Location

Research Site

New Brunswick, New Jersey, 08903, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Greenville, South Carolina, 29607, United States

Location

Research Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Research Site

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Créteil, 94010, France

Location

Research Site

Paris, 75475, France

Location

Research Site

Dresden, 01307, Germany

Location

Research Site

Ulm, 89081, Germany

Location

Research Site

Seville, Andalusia, 41013, Spain

Location

Research Site

Salamanca, Castille and León, 37007, Spain

Location

Research Site

Barcelona, Catalonia, 08003, Spain

Location

Research Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Research Site

A Coruña, Galicia, 15006, Spain

Location

Research Site

Valencia, Valencia, 46026, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Bristol, BS2 8ED, United Kingdom

Location

Research Site

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Katz DA, Morris JD, Chu MP, David KA, Thieblemont C, Morley NJ, Khan SS, Viardot A, Martin Garcia-Sancho A, Rodriguez-Garcia G, Bastos-Oreiro M, Lee ST, Kormany W, Chen Y, Wong HL, Anderson AA, Katlinskaya Y, Avilion AA, Dai T, Gonzalez-Barca E. Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL. Leuk Lymphoma. 2022 Sep;63(9):2063-2073. doi: 10.1080/10428194.2022.2064981. Epub 2022 May 3.

  PMID: 35503708 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

blinatumomab; Dexamethasone; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: January 18, 2017
• Study Start: March 13, 2017
• Primary Completion: April 4, 2019
• Study Completion: October 28, 2019
• Last Updated: September 14, 2020
• Results First Posted: March 26, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

FR (2); DE (2); ES (7); CA (3); US (8); GB (2)