Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

May 22, 2022 updated by: Craig Portell, MD

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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:
  • PCI-32765
  • GDC-0199
  • venetoclax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Dose Limiting Toxicities
Time Frame: 30 Days Following Start of Treatment
30 Days Following Start of Treatment

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Craig Portell, MD

Collaborators

AbbVie

Investigators

  • Study Chair: Craig A Portell, MD, University of Virginia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

May 1, 2021

Study Completion (Actual)

May 1, 2021

Study Registration Dates

First Submitted

March 6, 2015

First Submitted That Met QC Criteria

April 13, 2015

First Posted (Estimate)

April 17, 2015

Study Record Updates

Last Update Posted (Actual)

May 24, 2022

Last Update Submitted That Met QC Criteria

May 22, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17983
  • ABT199-MCL-UVA-001 (Other Identifier: University of Virginia)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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