Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

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

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).

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.

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.