A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma

NCT ID: NCT01992653

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-29
• Study Completion Date: 2018-12-19

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.

Conditions

Lymphoma, Non Hodgkin

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Polatuzumab Vedotin (1.4mg) + G-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Polatuzumab Vedotin (1.0mg) + R-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin (1.8mg) + G-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Polatuzumab Vedotin (1.4mg) + R-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin (1.8mg) + R-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin (2.4mg) + R-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

Cyclophosphamide

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.

Intervention Type: DRUG

Doxorubicin

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Intervention Type: DRUG

Obinutuzumab

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.

Intervention Type: DRUG

Polatuzumab Vedotin

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.

Intervention Type: DRUG

Prednisolone

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.

Intervention Type: DRUG

Prednisone

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.

Intervention Type: DRUG

Rituximab

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Intervention Type: DRUG

Other Intervention Names

Gazyva/Gazyvaro; DCDS4501A; MabThera/Rituxan

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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)
• Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Positive for hepatitis B or hepatitis C infection
• Prior radiotherapy to the mediastinal/pericardial region
• Pregnant or lactating women
• Recent major surgery within 6 weeks before the start of Cycle 1 Day 1

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Greeley, Colorado, United States

Washington University; Pediatrics

St Louis, Missouri, United States

Northwest Cancer Specialists

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Willamette Valley Clinical Studies; Cancer Institute

Springfield, Oregon, United States

Blue Ridge Cancer Care

Roanoke, Virginia, United States

Hopital Henri Mondor, Unite Hemopathies lymphoides

Créteil, , France

Hopital Claude Huriez - CHU Lille; Service des maladies du sang

Lille, , France

Centre Hospitalier Lyon Sud; Hematolgie

Pierre-Bénite, , France

Centre Henri Becquerel; Hematologie

Rouen, , France

Countries

United States; France

References

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.

Reference Type: DERIVED

PMID: 32770353 (View on PubMed)

Tilly 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.

Reference Type: DERIVED

PMID: 31101489 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2013-003541-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29044

Identifier Type: -

Identifier Source: org_study_id