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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 (POLARIX)

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ClinicalTrials.gov Identifier: NCT03274492
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug: Polatuzumab Vedotin Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Vincristine Placebo Drug: Prednisone Drug: Polatuzumab vedotin Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 875 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 16, 2017
Estimated Primary Completion Date : December 17, 2019
Estimated Study Completion Date : April 15, 2023


Arm Intervention/treatment
Experimental: R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin
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.
Drug: Polatuzumab Vedotin
Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
Other Name: DCDS4501A; anti-CD79b-VC-MMAE

Drug: Rituximab
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Cyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Doxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Vincristine Placebo
Placebo matching to vincristine will be administered as per the schedule specified in the respective arm.

Drug: Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.

Placebo Comparator: R-CHOP plus Polatuzumab Vedotin Placebo
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.
Drug: Rituximab
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Cyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Doxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Vincristine
Vincristine IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.

Drug: Polatuzumab vedotin Placebo
Placebo matching to polatuzumab vedotin will be administered as per the schedule specified in the respective arm.




Primary Outcome Measures :
  1. 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) ]

Secondary Outcome Measures :
  1. 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]) ]
  2. 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) ]
  3. 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) ]
  4. Overall Survival [ Time Frame: From randomization until death from any cause (up to approximately 65 months) ]
  5. 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]) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. Percentage of Participants With adverse Events (AEs) [ Time Frame: From randomization to the end of study (up to approximately 65 months) ]
  16. 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) ]
  17. 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) ]
  18. 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) ]
  19. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274492


Contacts
Contact: Reference Study ID Number: GO39942 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03274492     History of Changes
Other Study ID Numbers: GO39942
2017-002023-21 ( EudraCT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: November 16, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Immunoconjugates
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors