A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
Status: | Completed |
---|---|
Conditions: | Lymphoma, Lymphoma |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 1/30/2019 |
Start Date: | November 29, 2013 |
End Date: | December 19, 2018 |
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
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.
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.
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 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
- Abnormal laboratory values
We found this trial at
11
sites
Cancer Care Centers of South Texas At Cancer Care Centers of South Texas, we are...
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University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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1624 South I Street
Tacoma, Washington 98405
Tacoma, Washington 98405
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