A Safety and Pharmacokinetics (PK) Study of Venetoclax in Participants With Non-Hodgkin's Lymphoma
Status: | Active, not recruiting |
---|---|
Conditions: | Lymphoma, Lymphoma |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 3/7/2019 |
Start Date: | November 17, 2013 |
End Date: | June 28, 2019 |
A Phase Ib/II, Open-Label Study Evaluating the Safety and Pharmacokinetics of GDC-0199 (ABT-199) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL
This is a multicenter, open-label, dose-finding study of venetoclax administered orally in
combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide,
doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's
Lymphoma (NHL). The study will consist of 2 stages: a dose-finding Phase Ib stage and a Phase
II expansion stage. In the Phase I portion of the study, participants will be randomized to
one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in
combination with G-CHOP (Arm B) and will explore the doses of venetoclax in combination with
R-CHOP and G-CHOP. The maximum tolerated dose (MTD) of venetoclax in combination with R-CHOP
and G-CHOP will be determined during the dose-finding stage. For the Phase II portion of the
study, the venetoclax dose for venetoclax + R-CHOP is on a non-continuous dosing schedule as
determined by the Phase Ib portion of the study based on safety and tolerability observed in
participants treated in the dose escalation portion of the study.
combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide,
doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's
Lymphoma (NHL). The study will consist of 2 stages: a dose-finding Phase Ib stage and a Phase
II expansion stage. In the Phase I portion of the study, participants will be randomized to
one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in
combination with G-CHOP (Arm B) and will explore the doses of venetoclax in combination with
R-CHOP and G-CHOP. The maximum tolerated dose (MTD) of venetoclax in combination with R-CHOP
and G-CHOP will be determined during the dose-finding stage. For the Phase II portion of the
study, the venetoclax dose for venetoclax + R-CHOP is on a non-continuous dosing schedule as
determined by the Phase Ib portion of the study based on safety and tolerability observed in
participants treated in the dose escalation portion of the study.
Inclusion Criteria:
General Inclusion Criteria:
- At least one bi-dimensionally measurable lesion on CT scan defined as more than (>)
1.5 centimeters (cm) in its longest dimension
- Confirmed availability of archival or freshly biopsied tumor tissue prior to study
enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Adequate hematologic function
- For female participants of childbearing potential, agreement to use highly effective
forms of contraception
Dose-Escalation Portion of the Study:
- Participants must have histologically confirmed B-cell NHL
- Participants must have never received previous R-CHOP treatment
- Any relapsed/refractory participants that are enrolled during the dose escalation
should have received only a single previous treatment regimen
Expansion Portion of the Study:
- Participants must have previously untreated cluster of differentiation (CD)
20-positive diffuse large, B-cell lymphoma
- International prognostic index (IPI) score must be 2-5
Exclusion Criteria:
General 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 receive any of the individual components of CHOP, rituximab or
obinutuzumab
- Prior anthracycline therapy
- Participants with ongoing corticosteroid use >30 mg per day of prednisone or
equivalent
- Participants with central nervous system (CNS) lymphoma
- Vaccination with live vaccines within 28 days prior to randomization
- Chemotherapy or other 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 disease
- Significant cardiovascular disease or significant pulmonary disease
- Left ventricular ejection fraction less than (<) 50% as defined by multiple-gated
acquisition (MUGA)
- 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 prior to Cycle 1 Day 1
- Received the following agents within 7 days prior to the first dose of venetoclax:
steroid therapy for anti-neoplastic intent; strong and moderate cytochrome P450 (CYP)
3A4 inhibitors or inducers; grapefruit/grapefruit products, seville oranges or star
fruit within 3 days prior to the first dose of venetoclax
- Clinically significant history of liver disease, including viral or other hepatitis,
current alcohol abuse, or cirrhosis
- Recent major surgery
- Women who are pregnant or lactating
Dose-Escalation Portion of the Study:
- Participants with confirmed mantle cell lymphoma (MCL) or small lymphocytic lymphoma
(SLL)
Expansion Portion of the Study:
- Participants with transformed lymphoma
- Prior therapy for NHL
We found this trial at
17
sites
3100 Plaza Properties Boulevard
Columbus, Ohio 43213
Columbus, Ohio 43213
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60 2nd Street
Hackensack, New Jersey 07601
Hackensack, New Jersey 07601
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Tennessee Oncology, PLLC Since 1976 Tennessee Oncology has been providing quality cancer care. In 2013,...
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Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Rochester, New York 14642
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