A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
Conditions
Lymphoma, B-Cell, Non-Hodgkin's Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, B-Cell - Lymphoma, Non-Hodgkin
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cyclophosphamide Type: Drug
Name: Doxorubicin Type: Drug
Name: Obinutuzumab Type: Drug
Name: Polatuzumab Vedotin Type: Drug
Name: Prednisone/Prednisolone Type: Drug
Name: Rituximab Type: Drug
Overall Status
Recruiting
Summary
This multicenter, open-label, dose-escalation study will evaluate the safety and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone in participants with non-Hodgkin's lymphoma. Cohort of participants will receive escalating doses of polatuzumab vedotin intravenously every 3 weeks in combination with standard doses of rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and oral prednisone. 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 rituximab-prednisone/prednisolone, cyclophosphamide, and doxorubicin (R-CHP) and obinutuzumab-prednisone/prednisolone, cyclophosphamide, and doxorubicin (G-CHP). The maximum tolerated dose (MTD) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD is determined, polatuzumab vedotin will be dosed at MTD -1 in combination with G-CHP to start the dose escalation of this combination. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP and G-CHP. The MTD of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD is determined, polatuzumab vedotin will be dosed at MTD -1 in combination with G-CHP to start the dose escalation of this combination.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 80 Years
Minimum Age: 60 Years
Gender: Both
Criteria: Inclusion Criteria:

All Participants:

- Adult participants, 60 to 80 years of age, inclusive

- At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeter (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)

Dose-Escalation Portion of the Study:

- Histologically confirmed B-cell non-Hodgkin's lymphoma (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-CD20 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)

- Age-adjusted-International Prognostic Index score of 2-3

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 >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

- 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)

- 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
Locations
Birmingham, Alabama, United States
Status: Recruiting
Gilbert, Arizona, United States
Status: Not yet recruiting
Detroit, Michigan, United States
Status: Recruiting
St. Louis, Missouri, United States
Status: Recruiting
Portland, Oregon, United States
Status: Active, not recruiting
Portland, Oregon, United States
Status: Recruiting
Springfield, Oregon, United States
Status: Recruiting
Blacksburg, Virginia, United States
Status: Not yet recruiting
Tacoma, Washington, United States
Status: Recruiting
Creteil, France
Status: Recruiting
Lille, France
Status: Recruiting
Pessac, France
Status: Recruiting
Pierre Benite, France
Status: Recruiting
Rennes, France
Status: Recruiting
Rouen, France
Status: Recruiting
Start Date
November 2013
Completion Date
February 2020
Sponsors
Genentech, Inc.
Source
Genentech, Inc.
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page