A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma
2 other identifiers
interventional
85
2 countries
11
Brief Summary
This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2013
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 28, 2013
CompletedFirst Posted
Study publicly available on registry
November 25, 2013
CompletedStudy Start
First participant enrolled
November 29, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 19, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 19, 2018
CompletedResults Posted
Study results publicly available
March 3, 2020
CompletedMarch 14, 2023
March 1, 2023
5.1 years
October 28, 2013
December 18, 2019
March 10, 2023
Conditions
Outcome Measures
Primary Outcomes (4)
Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Baseline up to 5 years
Number of Participants With Adverse Events in Non-DLBCL Population
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Baseline up to 5 years
Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Number of Participants With DLTs in Non-DLBCL Population
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Secondary Outcomes (23)
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population
At the end of treatment (Month 6)
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
At the end of treatment (Month 6)
Number of Participants With Anti-Polatuzumab Vedotin Antibodies
Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days)
Number of Participants With Anti-Obinutuzumab Antibodies
Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days)
Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin
Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
- +18 more secondary outcomes
Study Arms (8)
Polatuzumab Vedotin (1.4mg) + G-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Polatuzumab Vedotin (1.0mg) + R-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Polatuzumab Vedotin (1.8mg) + G-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Polatuzumab Vedotin (1.4mg) + R-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Polatuzumab Vedotin (1.8mg) + R-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Polatuzumab Vedotin (2.4mg) + R-CHP
EXPERIMENTALDose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP
EXPERIMENTALDose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
EXPERIMENTALDose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Interventions
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m\^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Eligibility Criteria
You may qualify if:
- All Participants:
- At least one bi-dimensionally measurable lesion, defined as greater than (\>) 1.5 centimeters (cm) in its longest dimension
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
- Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of \<1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 5 months after the last dose of study drug
- Dose-Escalation Portion of the Study:
- Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible
- No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation \[CD\] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen)
- No prior treatment with anthracyclines
- Expansion Portion of the Study:
- Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)
- International Prognostic Index (IPI) score of 2-5
You may not qualify if:
- Dose-Escalation Portion of the Study:
- Diagnosis of primary mediastinal DLBCL
- Expansion Portion of the Study:
- Participants with transformed lymphoma
- Prior therapy for NHL
- All Participants:
- Prior stem cell transplant
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Contraindication to receive any of the individual components of R-CHP or G-CHP
- Current Grade greater than (\>) 1 peripheral neuropathy
- Ongoing corticosteroid use of \>30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (\</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
- Primary central nervous system (CNS) lymphoma
- Vaccination with live vaccines within 6 months before Cycle 1 Day 1
- History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (\</=) 5 years before enrollment
- Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (11)
The University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner MD Anderson Cancer Center
Greeley, Colorado, 85234, United States
Washington University; Pediatrics
St Louis, Missouri, 63110, United States
Northwest Cancer Specialists
Portland, Oregon, 97210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Willamette Valley Clinical Studies; Cancer Institute
Springfield, Oregon, 97477, United States
Blue Ridge Cancer Care
Roanoke, Virginia, 24014, United States
Hopital Henri Mondor, Unite Hemopathies lymphoides
Créteil, 94010, France
Hopital Claude Huriez - CHU Lille; Service des maladies du sang
Lille, 59037, France
Centre Hospitalier Lyon Sud; Hematolgie
Pierre-Bénite, 69495, France
Centre Henri Becquerel; Hematologie
Rouen, 76038, France
Related Publications (2)
Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
PMID: 32770353DERIVEDTilly H, Morschhauser F, Bartlett NL, Mehta A, Salles G, Haioun C, Munoz J, Chen AI, Kolibaba K, Lu D, Yan M, Penuel E, Hirata J, Lee C, Sharman JP. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019 Jul;20(7):998-1010. doi: 10.1016/S1470-2045(19)30091-9. Epub 2019 May 14.
PMID: 31101489DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Genentech, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 28, 2013
First Posted
November 25, 2013
Study Start
November 29, 2013
Primary Completion
December 19, 2018
Study Completion
December 19, 2018
Last Updated
March 14, 2023
Results First Posted
March 3, 2020
Record last verified: 2023-03