Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)

NCT ID: NCT02951156

Last Updated: 2020-12-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-16

Study Completion Date

2019-12-02

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Study B9991011 is a multi-center, international, randomized, open label, 2 component (Phase 1b followed by Phase 3), parallel-arm study of avelumab in combination with various agents for the treatment of Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The target study population of this Phase 1b/3 registrational study is patients with R/R DLBCL who have completed at least 2 (but not more than 4) lines of prior rituximab-containing multi-agent chemotherapy, and/or in whom autologous stem cell transplant (ASCT) has failed, or who are not candidates for ASCT or who are not eligible for intensive chemotherapy. Patients who are ineligible for intensive second line chemotherapy must have received at least one prior rituximab-containing combination chemotherapy regimen. The study will assess the safety, efficacy, pharmacokinetics (PK), immunogenicity of the 3 avelumab-based combination regimens tested, and collect patient reported outcome (PRO) data.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diffuse Large B-Cell Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase 1b Arm A

avelumab/utomilumab/rituximab

Group Type EXPERIMENTAL

Avelumab

Intervention Type BIOLOGICAL

Investigational fully human anti-PD-L1 monoclonal antibody

Utomilumab

Intervention Type BIOLOGICAL

Investigational, fully human IgG2 CD 137/4-1BB agonist

Rituximab

Intervention Type BIOLOGICAL

CD20-directed cytolytic antibody

Phase 1b Arm B

avelumab/utomilumab/azacitidine

Group Type EXPERIMENTAL

Avelumab

Intervention Type BIOLOGICAL

Investigational fully human anti-PD-L1 monoclonal antibody

Utomilumab

Intervention Type BIOLOGICAL

Investigational, fully human IgG2 CD 137/4-1BB agonist

Azacitidine

Intervention Type OTHER

Antimetabolite antineoplastic agent and demethylation agent.

Phase 1b Arm C

avelumab/rituximab/bendamustine

Group Type EXPERIMENTAL

Avelumab

Intervention Type BIOLOGICAL

Investigational fully human anti-PD-L1 monoclonal antibody

Rituximab

Intervention Type BIOLOGICAL

CD20-directed cytolytic antibody

Bendamustine

Intervention Type DRUG

Alkylating drug

Phase 3 Arm D (selected from Phase 1b)

Selected regimen from Phase 1b component which may be i) avelumab/utomilumab/rituximab OR ii) avelumab/rituximab/azacitidine OR iii) avelumab/rituximab/bendamustine

Group Type EXPERIMENTAL

Avelumab

Intervention Type BIOLOGICAL

Investigational fully human anti-PD-L1 monoclonal antibody

Utomilumab

Intervention Type BIOLOGICAL

Investigational, fully human IgG2 CD 137/4-1BB agonist

Rituximab

Intervention Type BIOLOGICAL

CD20-directed cytolytic antibody

Azacitidine

Intervention Type OTHER

Antimetabolite antineoplastic agent and demethylation agent.

Bendamustine

Intervention Type DRUG

Alkylating drug

Phase 3 Arm E

Investigator's Choice of either rituximab/bendamustine or rituximab/gemcitabine/oxaliplatin

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type BIOLOGICAL

CD20-directed cytolytic antibody

Bendamustine

Intervention Type DRUG

Alkylating drug

Gemcitabine

Intervention Type DRUG

Nucleoside analogue

Oxaliplatin

Intervention Type DRUG

Platinum-based drug

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Avelumab

Investigational fully human anti-PD-L1 monoclonal antibody

Intervention Type BIOLOGICAL

Utomilumab

Investigational, fully human IgG2 CD 137/4-1BB agonist

Intervention Type BIOLOGICAL

Rituximab

CD20-directed cytolytic antibody

Intervention Type BIOLOGICAL

Azacitidine

Antimetabolite antineoplastic agent and demethylation agent.

Intervention Type OTHER

Bendamustine

Alkylating drug

Intervention Type DRUG

Gemcitabine

Nucleoside analogue

Intervention Type DRUG

Oxaliplatin

Platinum-based drug

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MSB0010718C PF-05082566 Rituxan Vidaza Treanda Gemzar Eloxatin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

-Any of the following as defined by the WHO, 2016 lymphoid neoplasm classifications and histologically confirmed:

* Diffuse large B-cell lymphoma (DLBCL), Not Otherwise Specified (NOS): Germinal center B-cell type (GCB), Activated B-cell type (ABC)
* High-grade B-cell lymphoma (HGBCL) NOS
* HGBCL with MYC and BCL2 and/or BCL6 rearrangements
* T-cell histocyte-rich large B-cell lymphoma
* EBV+ DLBCL, NOS
* HHV8+ DLBCL, NOS

Relapsed or refractory disease following at least 2 lines (and a maximum of 4 lines) of prior rituximab containing multi-agent chemotherapy which may include an autologous stem cell transplantation unless patients are not considered suitable for intensive second-line chemotherapy or autologous stem cell transplantation. Patients who are ineligible for intensive second line chemotherapy,must have received at least one prior rituximab-containing combination chemotherapy regimen. Patients who are ineligible for intensive second line chemotherapy, must have received at least one prior rituximab-containing combination chemotherapy regimen.

* Baseline measurable disease with at least 1 bi dimensional lesion with longest diameter (LDi) \>1.5cm on CT scan which is FDG avid on PET scan.
* A biopsy (archived or Screening/recent) will be collected at Screening.
* At least 18years of age (or ≥20 years in Japan).
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

Exclusion Criteria

* Active central nervous system (CNS) lymphoma.
* Prior organ transplantation including prior allogeneic SCT.
* Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody, or drug specifically targeting T cell co stimulatory or immune checkpoint pathways).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

EMD Serono

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope

Duarte, California, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Norton Diagnostic Center - Dupont

Louisville, Kentucky, United States

Site Status

Norton Women's and Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Parexel International

Billerica, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

North Shore Hematology Oncology Associates

East Setauket, New York, United States

Site Status

St. George Hospital

Kogarah, New South Wales, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

Cancer Clinical Trials Centre, Austin Health, Level 4

Heidelberg, Victoria, Australia

Site Status

Genesis Care

Heidelberg, Victoria, Australia

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Farmacia Studi Clinici

Rozzano, MI, Italy

Site Status

Istituto Clinico Humanitas

Rozzano, MI, Italy

Site Status

Malopolskie Centrum Medyczne S.C.

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli

Lublin, Lublin Voivodeship, Poland

Site Status

Nzoz McD Voxel Osrodek Pet-Tk-Nmr

Krakow, , Poland

Site Status

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli Oddzial Hematologiczny

Lublin, , Poland

Site Status

NU-MED Centrum Diagnostyki i Terapii Onkologicznej Zamosc Sp. z o.o.

Zamość, , Poland

Site Status

Samsung Medical Center Clinical Trial Pharmacy

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital San Pedro de Alcantara

Cáceres, , Spain

Site Status

Centro de Investigación Medicina Especializada Sanitaria (CIMES)

Málaga, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

The Christie Pathology Partnership

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Czechia Denmark France Netherlands Sweden United States Australia Belgium Italy Poland South Korea Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Hawkes EA, Phillips T, Budde LE, Santoro A, Saba NS, Roncolato F, Gregory GP, Verhoef G, Offner F, Quero C, Radford J, Giannopoulos K, Stevens D, Thall A, Huang B, Laird AD, Sandner R, Ansell SM. Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study. Target Oncol. 2021 Nov;16(6):761-771. doi: 10.1007/s11523-021-00849-8. Epub 2021 Oct 23.

Reference Type DERIVED
PMID: 34687398 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://pmiform.com/clinical-trial-info-request?StudyID=B9991011

To obtain contact information for a study center near you, click here.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2016-002904-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B9991011

Identifier Type: -

Identifier Source: org_study_id