Clinical Trials /

Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

NCT02419560

Description:

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).

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17983
  • SECONDARY ID: ABT199-MCL-UVA-001
  • NCT ID: NCT02419560

Conditions

  • Lymphoma, Mantle-Cell
  • Recurrent Lymphoma, Mantle-Cell

Interventions

DrugSynonymsArms
ABT-199 and Ibrutinib CombinationGDC-0199, venetoclax, PCI-32765ABT-199 and Ibrutinib Combination

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ABT-199 and Ibrutinib CombinationExperimentalParticipants will take ABT-199 (dose 100-400 mg) and Ibrutinib (dose 280-560 mg).
  • ABT-199 and Ibrutinib Combination

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose Limiting Toxicities
Time Frame:30 Days Following Start of Treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence and Severity of Adverse Events
Time Frame:Through 30 Days Following the Last Treatment
Safety Issue:
Description:
Measure:Overall Response Rate
Time Frame:Every Year Until Death; an Average of 2 Years
Safety Issue:
Description:
Measure:Complete Response Rate
Time Frame:Every Year Until Death; an Average of 2 Years
Safety Issue:
Description:
Measure:Progression-Free Survival
Time Frame:Every Year Until Death; an Average of 2 Years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Every Year Until Death; an Average of 2 Years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Craig Portell, MD

Trial Keywords

  • Relapsed
  • Laboratory biomarker research
  • Pharmacologic study
  • Bruton's tyrosine kinase inhibitor
  • BCL-2 inhibitor

Last Updated

May 23, 2018