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).
Active, not recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Polatuzumab Vedotin | DCDS4501A; anti-CD79b-VC-MMAE | R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin |
| Rituximab | R-CHOP plus Polatuzumab Vedotin Placebo | |
| Cyclophosphamide | R-CHOP plus Polatuzumab Vedotin Placebo | |
| Doxorubicin | R-CHOP plus Polatuzumab Vedotin Placebo | |
| Vincristine | R-CHOP plus Polatuzumab Vedotin Placebo | |
| Vincristine Placebo | R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin | |
| Prednisone | R-CHOP plus Polatuzumab Vedotin Placebo | |
| Polatuzumab vedotin Placebo | R-CHOP plus Polatuzumab Vedotin Placebo |
| Name | Type | Description | Interventions |
|---|---|---|---|
| R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin | Experimental | Participants 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. |
|
| R-CHOP plus Polatuzumab Vedotin Placebo | Placebo Comparator | Participants 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. |
|
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
- Female participants: Agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive methods and refrain from donating eggs.
- Male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use a condom and agreement to refrain from donating sperm.
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 |
| 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: |
| 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: |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
May 26, 2021
