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A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Diffuse Large B-Cell Lymphoma

NCT03274492

Description:

This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP versus R-CHOP in participants with previously untreated diffuse large B-cell lymphoma (DLBCL).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Diffuse Large B-Cell Lymphoma
  • Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of Polatuzumab Vedotin in Combination With Rituximab and CHP (R-CHP) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO39942
  • SECONDARY ID: 2017-002023-21
  • NCT ID: NCT03274492

Conditions

  • Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
Polatuzumab VedotinDCDS4501A; anti-CD79b-VC-MMAER-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
RituximabR-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
CyclophosphamideR-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
DoxorubicinR-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
VincristineR-CHOP plus Polatuzumab Vedotin Placebo
Vincristine PlaceboR-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
PrednisoneR-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
Polatuzumab vedotin PlaceboR-CHOP plus Polatuzumab Vedotin Placebo

Purpose

This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP versus R-CHOP in participants with previously untreated diffuse large B-cell lymphoma (DLBCL).

Trial Arms

NameTypeDescriptionInterventions
R-CHP plus Vincristine Placebo plus Polatuzumab VedotinExperimentalParticipants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV), placebo for vincristine IV, rituximab 375 milligrams per square meter (mg/m^2) IV, cyclophosphamide 750 mg/m^2 IV, and doxorubicin 50 mg/m^2 IV on Day 1 and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m^2 IV will be administered as monotherapy in Cycles 7 and 8.
  • Polatuzumab Vedotin
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine Placebo
  • Prednisone
R-CHOP plus Polatuzumab Vedotin PlaceboPlacebo ComparatorParticipants will receive placebo for polatuzumab vedotin, rituximab 375 mg/m^2 IV, cyclophosphamide 750 mg/m^2 IV, doxorubicin 50 mg/m^2 IV, and vincristine 1.4 mg/m^2 IV (maximum 2 milligrams per dose [mg/dose]) on Day 1 and prednisone 100 mg/day PO on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m^2 IV will be administered as monotherapy in Cycles 7 and 8.
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Polatuzumab vedotin Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Previously untreated participants with cluster of differentiation 20 (CD20)-positive
             DLBCL, including one of the following diagnoses by 2016 World Health Organization
             (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS)
             including germinal center B-cell type, activated B-cell type; T-cell/histiocyte-rich
             large B-cell lymphoma; Epstein-Barr virus-positive DLBCL, NOS; anaplastic lymphoma
             kinase (ALK)-positive large B-cell lymphoma; human herpesvirus-8 (HHV8)-positive
             DLBCL, NOS; High-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or
             B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma);
             High-grade B-cell lymphoma, NOS

          -  Availability of archival or freshly collected tumor tissue before study enrolment

          -  International Prognostic Index (IPI) score of 2-5

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

          -  Life expectancy greater than or equal to (>/=)12 months

          -  Left ventricular ejection fraction (LVEF) >/= 50 percent (%) on cardiac multiple-gated
             acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

          -  Adequate hematologic function

        Exclusion Criteria:

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies or known sensitivity or allergy to murine products

          -  Contraindication to any of the individual components of CHOP, including prior receipt
             of anthracyclines

          -  Prior organ transplantation

          -  Current Grade greater than (>) 1 peripheral neuropathy by clinical examination

          -  Demyelinating form of Charcot-Marie-Tooth disease

          -  History of indolent lymphoma

          -  History of follicular lymphoma grade 3B

          -  B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and
             classical Hodgkin lymphoma (grey-zone lymphoma)

          -  Primary mediastinal (thymic) large B-cell lymphoma

          -  Burkitt lymphoma

          -  Prior treatment with cytotoxic drugs within 5 years of screening for any condition
             (example [e.g.], cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody

          -  Prior use of any monoclonal antibody within 3 months of the start of Cycle 1

          -  Prior therapy for DLBCL, with the exception of nodal biopsy

          -  Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than
             lymphoma symptom control

          -  Participants with central nervous system (CNS) lymphoma (primary or secondary
             involvement), primary effusion DLBCL, and primary cutaneous DLBCL

          -  Vaccination with live vaccines within 28 days prior to the start of Cycle 1

          -  Any investigational therapy within 28 days prior to the start of Cycle 1

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results

          -  Evidence of significant, uncontrolled, concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease or pulmonary disease

          -  Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for
             diagnosis

          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically
             significant in the investigator's opinion, including complete left bundle branch
             block, second- or third-degree heart block, or evidence of prior myocardial infarction

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment or significant
             infections within 2 weeks before the start of Cycle 1

          -  Clinically significant liver disease, including active viral or other hepatitis,
             current alcohol abuse, or cirrhosis

          -  Prior radiotherapy to the mediastinal/pericardial region

          -  Participants with suspected active or latent tuberculosis

          -  Positive test results for chronic hepatitis B and hepatitis C infection

          -  Known history of human immunodeficiency virus (HIV) seropositive status

          -  Positive results for the human T-lymphotrophic 1 virus (HTLV-1)

          -  Participants with a history of progressive multifocal leukoencephalopathy
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 38 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With Complete Response (CR) as Assessed by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Blinded Independent Central Review (BICR)
Time Frame:End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days] [up to Week 32])
Safety Issue:
Description:
Measure:Event-Free Survival-Efficacy (EFSeff) as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:From randomization to first occurrence of disease progression/relapse;or death from any cause;or other primary efficacy reason that leads to initiation of any non-protocol specified antilymphoma treatment(NALT);or residual disease(up to approx 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants Who are Progression Free as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:24 months after enrollment (up to approximately 65 months)
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:From randomization until death from any cause (up to approximately 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants With CR as Assessed by FDG-PET by Investigator
Time Frame:End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days] [up to Week 32])
Safety Issue:
Description:
Measure:Disease-Free Survival (DFS) as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:From the date of first occurrence of a documented CR to the date of relapse or death from any cause (up to approximately 65 months)
Safety Issue:
Description:
Measure:Duration of Response as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:From the date of first occurrence of a documented CR or partial response (PR) to the date of progression, relapse, or death from any cause (up to approximately 65 months)
Safety Issue:
Description:
Measure:Event-Free Survival-All Causes (EFSall) as Assessed by the Investigator, Using the Lugano Response Criteria for Malignant Lymphoma
Time Frame:From randomization to disease progression or relapse, or death from any cause, or initiation of any NALT (up to approximately 65 months)
Safety Issue:
Description:
Measure:Time to Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue
Time Frame:Day 1 of Cycles 1, 2, 3 and 5 (Cycle length=21 days); treatment completion visit (TCV)/early treatment termination visit (ETTV) (up to approximately 32 weeks); post-treatment follow-up (FU) visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Time to Deterioration in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)
Time Frame:Day 1 of Cycles 1, 2, 3 and 5 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-C30 Physical Functioning and Fatigue
Time Frame:Day 1 of Cycles 1, 2, 3 and 5 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants Achieving Meaningful Improvement in FACT-Lym LymS
Time Frame:Day 1 of Cycles 1, 2, 3 and 5 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:EORTC QLQ-C30 Treatment-Related Symptoms Score
Time Frame:Day 1 of Cycles 1, 2, 3 and 5 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Peripheral Neuropathy Score
Time Frame:Day 1 of Cycles 1-8 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants With adverse Events (AEs)
Time Frame:From randomization to the end of study (up to approximately 65 months)
Safety Issue:
Description:
Measure:Serum Concentration of Total Polatuzumab Vedotin
Time Frame:Pre-infusion (0 hour [hr]), 0.5 hr post-infusion (infusion duration=90 minutes [min]) on Day 1 of Cycle 1 and 4 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Plasma Concentration of Polatuzumab Vedotin Conjugate (Antibody-Conjugated Mono-Methyl Auristatin E [acMMAE])
Time Frame:0.5 hr post-infusion (infusion duration=90 min) on Day 1 of Cycle 1 and 4 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
Time Frame:0.5 hr post-infusion (infusion duration=90 min) on Day 1 of Cycle 1 and 4 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-Drug Antibody (ADA) to Polatuzumab Vedotin
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 and 4 (Cycle length=21 days); TCV/ETTV (up to approximately 32 weeks); post-treatment FU visit (up to approximately 65 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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