Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adults With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

NCT ID: NCT03340766

Last Updated: 2024-10-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-16

Study Completion Date

2023-08-14

Brief Summary

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The primary objective of the study is to determine the maximum tolerated dose (MTD) of blinatumomab in combination with pembrolizumab in adults with relapsed or refractory (r/r) DLBCL.

Detailed Description

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The study was planned as 2 parts:

* Part 1 will test the safety of up to 3 different blinatumomab target dose levels in combination with pembrolizumab in a rolling 6 design. A Dose Level Review Team (DLRT) will review the safety data to evaluate possible drug effects and dose-limiting toxicities (DLTs).
* Part 2 will consist of an expansion cohort to assess pharmacokinetics (PK), safety, and preliminary efficacy data at the chosen target dose. The part 2 dose will be determined by the totality of the clinical data from part 1 as determined by the DLRT.

Based on the results from Part 1, a decision was made not to proceed with Part 2 of this study.

Secondary objectives of the study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of blinatumomab in combination with pembrolizumab. Tumor response will be evaluated according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al, 2007). With implementation of Protocol Amendment 5, response will also be assessed according to the Lugano Classification (Cheson et al, 2014). Only participants enrolled after implementation of Protocol Amendment 5 (03 December 2019) will have tumor assessments using the Lugano criteria.

Conditions

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Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab

Participants received blinatumomab administered as a continuous intravenous infusion (CIVI) for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days then 28 µg/day for the remaining days of treatment.

Starting on Day 15 participants also received 200 mg pembrolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) until disease progression or for up to 35 cycles.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Pembrolizumab

Intervention Type DRUG

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab

Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 56 µg/day for the remaining days of treatment.

Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Pembrolizumab

Intervention Type DRUG

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab

Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 112 µg/day for the remaining days of treatment.

Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Pembrolizumab

Intervention Type DRUG

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Expansion Cohort

This cohort will test the maximum tolerated dose of blinatumomab in combination with pembrolizumab identified in Part 1 of the study.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Pembrolizumab

Intervention Type DRUG

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Interventions

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Blinatumomab

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Intervention Type DRUG

Pembrolizumab

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Intervention Type DRUG

Other Intervention Names

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Blincyto AMG 103 Formerly known as MT103 or bscCD19xCD3 Keytruda MK-3475

Eligibility Criteria

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Inclusion Criteria

* Have histologically confirmed diffuse large B-cell lymphoma that is either:
* Refractory after at least one regimen of systemic chemotherapy and/or targeted therapy, or
* In first or later relapse if have received at least 2 systemic regimens since time of diagnosis, or
* Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT) with adequate organ function after proximity to transplantation time exclusions
* Have measurable disease
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Life expectancy of ≥ 12 weeks in the opinion of the Investigator
* Biopsy proven DLBCL (biopsy proven at least at primary diagnosis of DLBCL)

Exclusion Criteria

* Richter's transformation (DLBCL arising in the setting of prior chronic lymphocytic leukemia) or primary mediastinal B cell lymphoma (PMBCL)
* History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
* Has a diagnosis of immunodeficiency or has received systemic steroid therapy (in excess of 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol specified therapy.
* Has undergone prior allogeneic HSCT:
* within the last 5 years OR
* greater than 5 years ago but has active graft versus host disease (GvHD) requiring systemic treatment.
* Has received autologous HSCT within 6 weeks prior to start of treatment.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

La Jolla, California, United States

Site Status

Research Site

Charleston, South Carolina, United States

Site Status

Research Site

Greenville, South Carolina, United States

Site Status

Research Site

Darlinghurst, New South Wales, Australia

Site Status

Research Site

St Leonards, New South Wales, Australia

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Adelaide, South Australia, Australia

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East Melbourne, Victoria, Australia

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Geelong, Victoria, Australia

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Melbourne, Victoria, Australia

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Research Site

Murdoch, Western Australia, Australia

Site Status

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Créteil, , France

Site Status

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Nantes, , France

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Research Site

Pierre-Bénite, , France

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Research Site

Heidelberg, , Germany

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Ulm, , Germany

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Würzburg, , Germany

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Maastricht, , Netherlands

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Rotterdam, , Netherlands

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Santander, Cantabria, Spain

Site Status

Research Site

Salamanca, Castille and León, Spain

Site Status

Research Site

Barcelona, Catalonia, Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Countries

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United States Australia France Germany Netherlands Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2016-002191-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PN348

Identifier Type: OTHER

Identifier Source: secondary_id

20150290

Identifier Type: -

Identifier Source: org_study_id

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