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)

Browse trials for

• Lymphoma 5,578
• Lymphoma, B-Cell 1,411
• Lymphoma, Large B-Cell, Diffuse 1,390

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 29 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Phase 1b Arm A

  avelumab/utomilumab/rituximab

  Biological: Avelumab · Biological: Utomilumab · Biological: Rituximab

• Experimental
  Phase 1b Arm B

  avelumab/utomilumab/azacitidine

  Biological: Avelumab · Biological: Utomilumab · Other: Azacitidine

• Experimental
  Phase 1b Arm C

  avelumab/rituximab/bendamustine

  Biological: Avelumab · Biological: Rituximab · Drug: 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

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

• Active comparator
  Phase 3 Arm E

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

  Biological: Rituximab · Drug: Bendamustine · Drug: Gemcitabine · Drug: Oxaliplatin

Interventions

• BiologicalAvelumab

  Investigational fully human anti-PD-L1 monoclonal antibody

  Also known as: MSB0010718C

• BiologicalUtomilumab

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

  Also known as: PF-05082566

• BiologicalRituximab

  CD20-directed cytolytic antibody

  Also known as: Rituxan

• OtherAzacitidine

  Antimetabolite antineoplastic agent and demethylation agent.

  Also known as: Vidaza

• DrugBendamustine

  Alkylating drug

  Also known as: Treanda

• DrugGemcitabine

  Nucleoside analogue

  Also known as: Gemzar

• DrugOxaliplatin

  Platinum-based drug

  Also known as: Eloxatin

Primary outcomes

1. 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.

   Time frame: Day 1 Cycle 1 up to 4 Weeks

2. 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.

   Time frame: 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

1. 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

   AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03,severity was graded as Grade 1:asymptomatic/mild symptoms,clinical/diagnostic observations only, intervention not indicated; Grade 2:moderate, minimal, local/noninvasive intervention indicated,limiting age-appropriate instrumental activities of daily life (ADL); Grade 3:severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to AE. TEAE was defined as events which occurred during on-treatment period beginning with first dose of study treatment through minimum (30 days + last dose of study treatment or start of new anti-cancer drug therapy). In this outcome measure participant with any TEAE of Grade 3 or above are reported.

   Time frame: 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)

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

   Laboratory parameters included hematological and biochemistry: Hematological parameters included: anemia, haemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cells decreased. Biochemistry parameters included alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatine kinase(cpk) increased, creatinine increased, gamma glutamyl transferase(ggt) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased,serum amylase increased.Test abnormalities were graded by NCI CTCAE version 4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. Number of participants with abnormalities of any grade were reported.

   Time frame: 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)

3. Number of Participants With Electrocardiogram (ECG) Abnormalities

   ECG abnormalities included: 1) QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF): increase from baseline greater than (\>) 30 millisecond (ms) or 60 ms; absolute value \>450 ms, \>480 ms and \>500 ms; 2) heart rate (HR): absolute value \<=50 beats per minute (bpm) and decrease from baseline \>=20 bpm; absolute value \>=120 bpm and increase from baseline \>=20 bpm; 3) PR interval: absolute value \>=220 ms and increase from baseline \>=20 ms; 4) QRS interval: absolute value \>=120 ms.

   Time frame: 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)

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

   Investigator assessed DOR: was defined for participants with OR as time from first documentation of OR to time of first documentation of disease progression/death due to any cause, whichever occurred first. CR: score of 1(no uptake above background),2(uptake \<=mediastinum),or 3(uptake \<mediastinum but \<=liver) with or without a residual mass on PET 5-PS,for lymph nodes extralymphatic sites;no new lesions;no evidence of FDG-avid disease in bone marrow. PR: \>=50% decrease in SPD of up to 6 of largest dominant lymph nodes,no increase in size of other nodes,liver,spleen volume,\>=50% decrease in SPD of hepatic splenic nodules,absence of other organ involvement,no new sites of disease. PD: appearance of new lesion more than 1.5 cm in any axis,at least a 50% increase from nadir in SPD/longest diameter of previous lesion/node. Data was censored on date of last adequate tumor assessment in participants with no event,started new anti-cancer therapy/had 2 or more missing assessments.

   Time frame: 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)

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

   TTR was defined for participants who achieved objective response as time from randomization to first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as a score of 1 (no uptake above background), 2 (uptake \<= mediastinum), or 3 (uptake \<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of 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 SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.

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

6. Disease Control Rate as Assessed by the Investigator Per Lugano Response Classification Criteria

   Disease control rate was defined as percentage of participants with disease control. Disease Control (DC) was defined as the best overall response of CR, PR, or stable disease (SD). CR: score of 1 (no uptake above background), 2 (uptake \<= mediastinum), or 3 (uptake less than \<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow. PR: \>=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 SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. SD: \<50% decrease in SDP of up to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease met. To qualify as a best overall response of SD, at least one SD assessment must be observed \>=6 weeks after start date and before disease progression.

   Time frame: 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)

7. Progression-Free Survival (PFS) as Assessed by the Investigator Per Lugano Response Classification Criteria

   Investigator assessed PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants who had no an event (PD or death), for participants who start a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing or inadequate post-baseline tumor assessment. Participants without an adequate baseline or post-baseline tumor assessment were censored on the date of randomization unless death occurred on or before the time of the second planned tumor assessment in which case the death was considered as an event.

   Time frame: 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)

8. Overall Survival

   Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

   Time frame: From the date of randomization to discontinuation from the study or death, whichever occurred first (maximum up to 36 months)

9. Concentration Verses Time Summary of Avelumab

   Time frame: 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

10. Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status

    ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

    Time frame: 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)

11. Number of Participants With Anti-Drug Antibodies (ADA) Against Rituximab by Never and Ever Positive Status

    ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

    Time frame: From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)

12. Number of Participants With Anti-Drug Antibodies (ADA) Against Utomilumab by Never and Ever Positive Status

    ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

    Time frame: From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)

13. Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status

    nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

    Time frame: From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)

14. Number of Participants With Neutralizing Antibodies (nAb) Against Rituximab by Never and Ever Positive Status

    nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

    Time frame: From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)

15. Number of Participants With Neutralizing Antibodies (nAb) Against Utomilumab by Never and Ever Positive Status

    nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

    Time frame: From the date of first study treatment up to 30 Days after the end of treatment (maximum up to 36 months)

16. Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline

    Percentage of Tumor and Immune Cells as Assessed by Immunohistochemistry at Baseline.

    Time frame: Screening (prior to first dose of study treatment)

17. Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status

    Number of participants with MRD positive, negative and not evaluable status were reported in this outcome measure.

    Time frame: Baseline, Day 1 of Cycle 3, 6, 9, 12 and 18

Baseline characteristics

Publications

• 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. PubMed 34687398 ↗

Study documents

• Study protocol · Dec 11, 2017
• Statistical analysis plan · Feb 12, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.