Clinical trial NCT02419560: Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL
Official title: Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Mantle-Cell
Recurrent Lymphoma, Mantle-Cell
Keywords: Relapsed
Laboratory biomarker research
Pharmacologic study
Bruton's tyrosine kinase inhibitor
BCL-2 inhibitor
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2015-04-17
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: 30 Days Following Start of Treatment
Secondary outcomes:
measure: Incidence and Severity of Adverse Events
timeFrame: Through 30 Days Following the Last Treatment
measure: Overall Response Rate
timeFrame: Every Year Until Death; an Average of 2 Years
measure: Complete Response Rate
timeFrame: Every Year Until Death; an Average of 2 Years
measure: Progression-Free Survival
timeFrame: Every Year Until Death; an Average of 2 Years
measure: Overall Survival
timeFrame: Every Year Until Death; an Average of 2 Years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Craig A Portell, MD
role: STUDY_CHAIR
References:
citation: 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.