Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

Sponsor

Craig Portell, MD (Other)

Overall Status

Completed

CT.gov ID

NCT02419560

Collaborator

AbbVie (Industry)

Enrollment

Locations

Arm

Actual Duration (Months)

9.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Mantle-Cell Recurrent Lymphoma, Mantle-Cell	Drug: ABT-199 and Ibrutinib Combination	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma

Actual Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

May 1, 2021

Actual Study Completion Date :

May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-199 and Ibrutinib Combination Participants will take ABT-199 (dose 100-400 mg) and Ibrutinib (dose 280-560 mg).	Drug: ABT-199 and Ibrutinib Combination Both are administered orally once daily. Other Names: GDC-0199 venetoclax PCI-32765

Arm

Intervention/Treatment

Experimental: ABT-199 and Ibrutinib Combination

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

Drug: ABT-199 and Ibrutinib Combination

Both are administered orally once daily.

Other Names:

GDC-0199

venetoclax

PCI-32765

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicities [30 Days Following Start of Treatment]

Secondary Outcome Measures

Incidence and Severity of Adverse Events [Through 30 Days Following the Last Treatment]
Overall Response Rate [Every Year Until Death; an Average of 2 Years]
Complete Response Rate [Every Year Until Death; an Average of 2 Years]
Progression-Free Survival [Every Year Until Death; an Average of 2 Years]
Overall Survival [Every Year Until Death; an Average of 2 Years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.
Subjects must have measurable or evaluable disease.
ECOG Performance Status of 0-2.
Must be referred for treatment with ibrutinib.
Must have adequate organ function.

Exclusion Criteria:

Subject is pregnant.
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.
Known CNS lymphoma.
Prior or current treatment with certain medications. Talk to Study Contact for specifics.
Subject is at high risk for TLS.
Subject has malabsorption syndrome or other condition which may affect an enteral route of administration.
Subject has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase.
Significant history of heart disease.
Subject has an active infection.
Known active Hepatitis B or Hepatitis C.
A serious uncontrolled medical disorder that in the opinion of the investigator would impair the ability of the subject to receive protocol therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	University of Virginia	Charlottesville	Virginia	United States	22908