Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

NCT ID: NCT02419560

Last Updated: 2022-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2021-05-31

Brief Summary

The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL).

Detailed Description

This is a multi-center, study which will be open at up to 4 clinical sites. The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The main criterion for eligibility is MCL with measurable disease which is relapsed or refractory to at least 1 chemotherapy-containing regimen and has not been previously treated with ibrutinib.

This dose finding study will use a continual reassessment method, which accounts for both toxicity and efficacy in combinations of agents, to determine the optimal combination of the approved treatment ibrutinib with the investigational agent ABT-199. This study will accrue patients in two stages. In the initial stage, subjects will be accrued to dosing cohorts of increasing dosages of ABT-199 in combination with ibrutinib. The modeling is initiated once 1 subject experiences a dose limiting toxicity (DLT). During the modeling stage, treatment assignments will be made based on model prediction.

Subjects will remain on treatment until progression or unacceptable toxicity, and will be monitored for safety during the treatment interval. Safety will be evaluated by incidence of adverse events and number of discontinuations due to AEs. Efficacy endpoints include Overall Response Rate (ORR), Complete Response Rate (CRR), minimal residual disease response rate, and survival (PFS and OS). The study will also include exploratory analysis of the gene expression pattern in subjects who progress on treatment.

Conditions

Lymphoma, Mantle-Cell; Recurrent Lymphoma, Mantle-Cell

Study Design

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

Study Groups

ABT-199 and Ibrutinib Combination

Participants will take ABT-199 (dose 100-400 mg) and Ibrutinib (dose 280-560 mg).

Group Type: EXPERIMENTAL

ABT-199 and Ibrutinib Combination

Intervention Type: DRUG

Both are administered orally once daily.

Interventions

ABT-199 and Ibrutinib Combination

Both are administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

GDC-0199; venetoclax; PCI-32765

Eligibility Criteria

Inclusion Criteria

1. Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.

2. Subjects must have measurable or evaluable disease.

3. ECOG Performance Status of 0-2.

4. Must be referred for treatment with ibrutinib.

5. Must have adequate organ function.

Exclusion Criteria

1. Subject is pregnant.

2. Prior malignancy (except nonmelanomatous skin cancer) unless disease free for a minimum of 2 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.

3. Known CNS lymphoma.

4. Prior or current treatment with certain medications. Talk to Study Contact for specifics.

5. Subject is at high risk for TLS.

6. Subject has malabsorption syndrome or other condition which may affect an enteral route of administration.

7. Subject has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase.

8. Significant history of heart disease.

9. Subject has an active infection.

10. Known active Hepatitis B or Hepatitis C.

11. A serious uncontrolled medical disorder that in the opinion of the investigator would impair the ability of the subject to receive protocol therapy.

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

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Craig Portell, MD

OTHER

Sponsor Role: lead

Responsible Party

Craig Portell, MD

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Craig A Portell, MD

Role: STUDY_CHAIR

University of Virginia

Locations

City of Hope

Duarte, California, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

References

Jayappa KD, Tran B, Gordon VL, Morris C, Saha S, Farrington CC, O'Connor CM, Zawacki KP, Isaac KM, Kester M, Bender TP, Williams ME, Portell CA, Weber MJ, Narla G. PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis. J Clin Invest. 2023 Jul 3;133(13):e155938. doi: 10.1172/JCI155938.

Reference Type: DERIVED

PMID: 37166997 (View on PubMed)

Portell CA, Wages NA, Kahl BS, Budde LE, Chen RW, Cohen JB, Varhegyi NE, Petroni GR, Williams ME. Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. Blood Adv. 2022 Mar 8;6(5):1490-1498. doi: 10.1182/bloodadvances.2021005357.

Reference Type: DERIVED

PMID: 34700344 (View on PubMed)

Other Identifiers

ABT199-MCL-UVA-001

Identifier Type: OTHER

Identifier Source: secondary_id

17983

Identifier Type: -

Identifier Source: org_study_id