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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02951156




Registration number
NCT02951156
Ethics application status
Date submitted
19/10/2016
Date registered
1/11/2016

Titles & IDs
Public title
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)
Scientific title
PHASE 1B/PHASE 3 MULTICENTER STUDY OF AVELUMAB (MSB0010718C) 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 (DLBCL) JAVELIN DLBCL
Secondary ID [1] 0 0
2016-002904-15
Secondary ID [2] 0 0
B9991011
Universal Trial Number (UTN)
Trial acronym
Javelin DLBCL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Avelumab
Treatment: Other - Utomilumab
Treatment: Other - Rituximab
Other interventions - Azacitidine
Treatment: Drugs - Bendamustine
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Oxaliplatin

Experimental: Phase 1b Arm A - avelumab/utomilumab/rituximab

Experimental: Phase 1b Arm B - avelumab/utomilumab/azacitidine

Experimental: Phase 1b Arm C - avelumab/rituximab/bendamustine

Experimental: 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

Active comparator: Phase 3 Arm E - Investigator's Choice of either rituximab/bendamustine or rituximab/gemcitabine/oxaliplatin


Treatment: Other: Avelumab
Investigational fully human anti-PD-L1 monoclonal antibody

Treatment: Other: Utomilumab
Investigational, fully human IgG2 CD 137/4-1BB agonist

Treatment: Other: Rituximab
CD20-directed cytolytic antibody

Other interventions: Azacitidine
Antimetabolite antineoplastic agent and demethylation agent.

Treatment: Drugs: Bendamustine
Alkylating drug

Treatment: Drugs: Gemcitabine
Nucleoside analogue

Treatment: Drugs: Oxaliplatin
Platinum-based drug

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicities (DLT)
Timepoint [1] 0 0
Day 1 Cycle 1 up to 4 Weeks
Primary outcome [2] 0 0
Objective Response Rate (ORR) as Assessed by Investigator Per Lugano Response Classification Criteria
Timepoint [2] 0 0
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 outcome [1] 0 0
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
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Participants With Electrocardiogram (ECG) Abnormalities
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Duration of Response (DOR) as Assessed by Investigator Per Lugano Response Classification Criteria
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Time to Tumor Response (TTR) as Assessed by Investigator Per Lugano Response Classification Criteria
Timepoint [5] 0 0
From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to 36 months)
Secondary outcome [6] 0 0
Disease Control Rate as Assessed by the Investigator Per Lugano Response Classification Criteria
Timepoint [6] 0 0
From the date of randomization to the first documentation of PD, study discontinuation, start of new anti-cancer therapy or death due to any cause, whichever occurred first (maximum up to 36 months)
Secondary outcome [7] 0 0
Progression-Free Survival (PFS) as Assessed by the Investigator Per Lugano Response Classification Criteria
Timepoint [7] 0 0
From the date of randomization to progression of disease, study discontinuation, censoring date or death due to any cause, whichever occurred first (up to 36 months)
Secondary outcome [8] 0 0
Overall Survival
Timepoint [8] 0 0
From the date of randomization to discontinuation from the study or death, whichever occurred first (maximum up to 36 months)
Secondary outcome [9] 0 0
Concentration Verses Time Summary of Avelumab
Timepoint [9] 0 0
1 hour Post dose Day 2 Cycle 1, 144 hour Post dose Day 8 of Cycle 1, 0 hour Post dose Day 16 of Cycle 1, Day 1 of Cycle 4 and Cycle 6
Secondary outcome [10] 0 0
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Timepoint [10] 0 0
Baseline: 2 hours pre-dose of first dose of avelumab, Post baseline: post first dose up to up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [11] 0 0
Number of Participants With Anti-Drug Antibodies (ADA) Against Rituximab by Never and Ever Positive Status
Timepoint [11] 0 0
From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [12] 0 0
Number of Participants With Anti-Drug Antibodies (ADA) Against Utomilumab by Never and Ever Positive Status
Timepoint [12] 0 0
From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [13] 0 0
Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
Timepoint [13] 0 0
From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [14] 0 0
Number of Participants With Neutralizing Antibodies (nAb) Against Rituximab by Never and Ever Positive Status
Timepoint [14] 0 0
From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [15] 0 0
Number of Participants With Neutralizing Antibodies (nAb) Against Utomilumab by Never and Ever Positive Status
Timepoint [15] 0 0
From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)
Secondary outcome [16] 0 0
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
Timepoint [16] 0 0
Screening (prior to first dose of study treatment)
Secondary outcome [17] 0 0
Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status
Timepoint [17] 0 0
Baseline, Day 1 of Cycle 3, 6, 9, 12 and 18

Eligibility
Key inclusion criteria
Key

-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.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. George Hospital - Kogarah
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
Cancer Clinical Trials Centre, Austin Health, Level 4 - Heidelberg
Recruitment hospital [4] 0 0
Genesis Care - Heidelberg
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
Belgium
State/province [8] 0 0
Gent
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Italy
State/province [10] 0 0
MI
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Poland
State/province [12] 0 0
Lubelskie
Country [13] 0 0
Poland
State/province [13] 0 0
Malopolskie
Country [14] 0 0
Poland
State/province [14] 0 0
Krakow
Country [15] 0 0
Poland
State/province [15] 0 0
Lublin
Country [16] 0 0
Poland
State/province [16] 0 0
Zamosc
Country [17] 0 0
Spain
State/province [17] 0 0
Caceres
Country [18] 0 0
Spain
State/province [18] 0 0
Cáceres
Country [19] 0 0
Spain
State/province [19] 0 0
Málaga
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
EMD Serono
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.