A Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Combination With Bendamustine/Rituximab (BR) in Subjects With Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT ID: NCT01594229

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-21
• Study Completion Date: 2020-07-14

Brief Summary

This is a Phase 1, open-label, multicenter study evaluating the safety, pharmacokinetic profile, and preliminary efficacy of ABT-199 in combination with Bendamustine/Rituximab in approximately 60 subjects with relapsed or refractory non-Hodgkin's lymphoma. This study will evaluate the safety and pharmacokinetic profile of ABT-199 in approximately 60 subjects when administered in combination with Bendamustine/Rituximab following a dose escalation scheme, with the objective of defining the dose limiting toxicity and the maximum tolerated dose.

Conditions

Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Non-Hodgkin's Lymphoma (NHL)

Group Type: EXPERIMENTAL

ABT-199

Intervention Type: DRUG

ABT-199 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study.

Rituximab

Intervention Type: DRUG

Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle.

Bendamustine

Intervention Type: DRUG

Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle.

Interventions

ABT-199

ABT-199 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study.

Intervention Type: DRUG

Rituximab

Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle.

Intervention Type: DRUG

Bendamustine

Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

• Subject (non-diffuse large B-cell lymphoma) must have relapsed or refractory non-Hodgkin's lymphoma, and require treatment in the opinion of the investigator.
• Subject with diffuse large B-cell lymphoma must have relapsed diffuse large B-cell lymphoma or must have progressed after salvage therapy (with or without standard chemotherapy) for diffuse large B-cell lymphoma. The subject must have received first line therapy with Rituximab-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) [or a similar standard rituximab-containing front-line chemoimmunotherapy regimen including, but not limited to Etoposide, Prednisone, Vincristine (Oncovin), Cyclophosphamide, Doxorubicin (Hydrochloride) + Rituximab (EPOCH + R); Rituximab, Cyclophosphamide, Etoposide, Procarbazine, Prednisone (RCEPP); Rituximab, Cyclophosphamide, Mitoxantrone (Novantrone), Vincristine (Oncovin), Prednisone (RCNOP); Dose-adjusted-Etoposide, Prednisone, Vincristine(Oncovin), Cyclophosphamide, Doxorubicin (Hydrocloride) (DA-EPOCH); and Rituximab, Cyclophosphamide, Etoposide, Vincristine (Oncovin), Prednisone (RCEOP)].
• Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.

• Subject has been diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma or mantle cell lymphoma (MCL).
• Subject has refractory diffuse large B-cell lymphoma, defined as meeting any of the following criteria:

• Subject progressed during or within 3 months of completion of a planned course of first-line therapy with Rituximab-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) or an equivalent regimen;
• Subject had no response (i.e., stable disease only) to first-line therapy with R-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) or an equivalent regimen;
• Subject progressed during or within 2 months of completion of their last planned course of salvage therapy with chemotherapy (with or without rituximab, may include autologous stem cell transplant).
• Subject has tested positive for human immunodeficiency virus (HIV).
• Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
• Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Ucsd /Id# 67350

La Jolla, California, United States

University of California, Los Angeles /ID# 67343

Los Angeles, California, United States

Emory University Hospital /ID# 67349

Atlanta, Georgia, United States

Georgia Regents University /ID# 67342

Augusta, Georgia, United States

Ingalls Memorial Hosp /ID# 67344

Harvey, Illinois, United States

Johns Hopkins University /ID# 67345

Baltimore, Maryland, United States

Henry Ford Health System /ID# 67346

Detroit, Michigan, United States

University of Texas MD Anderson Cancer Center /ID# 69222

Houston, Texas, United States

Countries

United States

References

de Vos S, Swinnen LJ, Wang D, Reid E, Fowler N, Cordero J, Dunbar M, Enschede SH, Nolan C, Petrich AM, Ross JA, Salem AH, Verdugo M, Agarwal S, Zhou L, Kozloff M, Nastoupil LJ, Flowers CR. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. Ann Oncol. 2018 Sep 1;29(9):1932-1938. doi: 10.1093/annonc/mdy256.

Reference Type: BACKGROUND

PMID: 30060083 (View on PubMed)

Other Identifiers

M12-630

Identifier Type: -

Identifier Source: org_study_id