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)

NCT02951156 | Terminated Phase 3 Results DMC

• 2 other identifiers: B99910112016-002904-15
• Study Type: interventional
• Target: 29
• Locations: 8 countries
• Sites: 29

Brief Summary

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).

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLT)

  AEs occurring in first 4 weeks of treatment,attributable to 1 of study drugs. Hematology:1)Grade 4 neutropenia,2)Grade \>=3 febrile neutropenia with single temperature of \>38.3 degrees Celsius (C)/sustained temperature of \>=38.0 degrees C for more than 1 hour with/without associated sepsis,3)Grade \>=3 neutropenic infection,4)Grade 4 thrombocytopenia/Grade 3 thrombocytopenia with clinically significant bleeding,5)Grade 4 anemia 6)Any grade \>=3 non-hematology toxicity except:transient Grade 3 flu like symptoms/fever controlled with standard medical management;transient Grade 3 fatigue,localized skin reactions/headache that resolves to Grade \<=1;Grade 3 nausea,vomiting/diarrhea resolved to Grade \<=1 in ˂72 hours after initiation of adequate medical management;Grade 3 skin toxicity resolved to Grade \<=1 in ˂7 days;tumor flare;Single laboratory values that are out of normal range,that have no clinical correlate and resolve to Grade \<=1 within 7 days with adequate medical management.

  Day 1 Cycle 1 up to 4 Weeks

• Objective Response Rate (ORR) as Assessed by Investigator Per Lugano Response Classification Criteria

  ORR was defined as percentage of participants with complete response (CR) or partial response (PR), as assessed by investigator per lugano response classification criteria. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\<=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \<=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. PR was defined as \>=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a \>=50% decrease in sum of products of diameters (SPD) of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.

  Randomization until date of PD, start of new anticancer therapy, discontinuation from study or death due to any cause, whichever occurred first (maximum up to 36 months)

Secondary Outcomes (17)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Greater Than or Equal to (>=) Grade 3, As Per National Cancer Institute Common Terminology Criteria For Adverse Events (NCI-CTCAE), Version 4.03

  From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

• Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03

  From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

• Duration of Response (DOR) as Assessed by Investigator Per Lugano Response Classification Criteria

  First response (CR or PR) to date of PD, start of new anti-cancer therapy, discontinuation from the study, censoring date or death due to any cause, whichever occurred first (maximum up to 36 months)

• Time to Tumor Response (TTR) as Assessed by Investigator Per Lugano Response Classification Criteria

  From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to 36 months)

Study Arms (5)

Phase 1b Arm A

EXPERIMENTAL

avelumab/utomilumab/rituximab

Biological: Avelumab; Biological: Utomilumab; Biological: Rituximab

Phase 1b Arm B

EXPERIMENTAL

avelumab/utomilumab/azacitidine

Biological: Avelumab; Biological: Utomilumab; Other: Azacitidine

Phase 1b Arm C

EXPERIMENTAL

avelumab/rituximab/bendamustine

Biological: Avelumab; Biological: Rituximab; Drug: Bendamustine

Phase 3 Arm D (selected from Phase 1b)

EXPERIMENTAL

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

Biological: Avelumab; Biological: Utomilumab; Biological: Rituximab; Other: Azacitidine; Drug: Bendamustine

Phase 3 Arm E

ACTIVE COMPARATOR

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

Biological: Rituximab; Drug: Bendamustine; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Avelumab BIOLOGICAL

Investigational fully human anti-PD-L1 monoclonal antibody

Also known as: MSB0010718C

Phase 1b Arm A; Phase 1b Arm B; Phase 1b Arm C; Phase 3 Arm D (selected from Phase 1b)

Utomilumab BIOLOGICAL

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

Also known as: PF-05082566

Phase 1b Arm A; Phase 1b Arm B; Phase 3 Arm D (selected from Phase 1b)

Rituximab BIOLOGICAL

CD20-directed cytolytic antibody

Also known as: Rituxan

Phase 1b Arm A; Phase 1b Arm C; Phase 3 Arm D (selected from Phase 1b); Phase 3 Arm E

Azacitidine OTHER

Antimetabolite antineoplastic agent and demethylation agent.

Also known as: Vidaza

Phase 1b Arm B; Phase 3 Arm D (selected from Phase 1b)

Bendamustine DRUG

Alkylating drug

Also known as: Treanda

Phase 1b Arm C; Phase 3 Arm D (selected from Phase 1b); Phase 3 Arm E

Gemcitabine DRUG

Nucleoside analogue

Also known as: Gemzar

Phase 3 Arm E

Oxaliplatin DRUG

Platinum-based drug

Also known as: Eloxatin

Phase 3 Arm E

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead
• EMD Serono: collaborator

Study Sites (29)

City of Hope

Duarte, California, 91010, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Norton Diagnostic Center - Dupont

Louisville, Kentucky, 40207, United States

Location

Norton Women's and Children's Hospital

Louisville, Kentucky, 40207, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Parexel International

Billerica, Massachusetts, 01821, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

North Shore Hematology Oncology Associates

East Setauket, New York, 11733, United States

Location

St. George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Cancer Clinical Trials Centre, Austin Health, Level 4

Heidelberg, Victoria, 3084, Australia

Location

Genesis Care

Heidelberg, Victoria, 3084, Australia

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Farmacia Studi Clinici

Rozzano, MI, 20089, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Malopolskie Centrum Medyczne S.C.

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli

Lublin, Lublin Voivodeship, 20-090, Poland

Location

Nzoz McD Voxel Osrodek Pet-Tk-Nmr

Krakow, 30-006, Poland

Location

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

Lublin, 20-090, Poland

Location

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

Zamość, 22-400, Poland

Location

Samsung Medical Center Clinical Trial Pharmacy

Seoul, 06351, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Centro de Investigación Medicina Especializada Sanitaria (CIMES)

Málaga, 29010, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Christie Pathology Partnership

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34687398 DERIVED

Related Links

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

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

avelumab; utomilumab; Rituximab; Azacitidine; Bendamustine Hydrochloride; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Butyrates; Acids, Acyclic; Carboxylic Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Coordination Complexes

Limitations and Caveats

Data for Phase 3 outcome measures were not collected as study was terminated early and phase 3 was not conducted.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: November 1, 2016
• Study Start: December 16, 2016
• Primary Completion: December 2, 2019
• Study Completion: December 2, 2019
• Last Updated: December 17, 2020
• Results First Posted: December 17, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); ES (3); AU (4); PL (5); KR (2); US (9); BE (2); GB (2)