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Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02419560
Recruitment Status : Unknown
Verified May 2018 by Craig Portell, MD, University of Virginia.
Recruitment status was:  Recruiting
First Posted : April 17, 2015
Last Update Posted : May 24, 2018
Information provided by (Responsible Party):
Craig Portell, MD, University of Virginia

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 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
Study Start Date : April 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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

Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities [ Time Frame: 30 Days Following Start of Treatment ]

Secondary Outcome Measures :
  1. Incidence and Severity of Adverse Events [ Time Frame: Through 30 Days Following the Last Treatment ]
  2. Overall Response Rate [ Time Frame: Every Year Until Death; an Average of 2 Years ]
  3. Complete Response Rate [ Time Frame: Every Year Until Death; an Average of 2 Years ]
  4. Progression-Free Survival [ Time Frame: Every Year Until Death; an Average of 2 Years ]
  5. Overall Survival [ Time Frame: Every Year Until Death; an Average of 2 Years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02419560

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Contact: Steve Fowler (434) 243-4730

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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Jaemee Bautistia    626-218-3033   
Principal Investigator: Robert Chen, MD         
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Alicia Escobar    404-778-4449   
Principal Investigator: Jonathon Cohen, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Christina Lapka    314-747-1798   
Principal Investigator: Brad Kahl, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Kristen Johnson    434-297-4185   
Contact: Kim Underwood    434-982-3947   
Principal Investigator: Craig Portell, MD         
Sub-Investigator: Mike Williams, MD         
Sponsors and Collaborators
Craig Portell, MD
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Study Chair: Craig A Portell, MD University of Virginia
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Responsible Party: Craig Portell, MD, Assistant Professor of Medicine, University of Virginia Identifier: NCT02419560    
Other Study ID Numbers: 17983
ABT199-MCL-UVA-001 ( Other Identifier: University of Virginia )
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018
Keywords provided by Craig Portell, MD, University of Virginia:
Laboratory biomarker research
Pharmacologic study
Bruton's tyrosine kinase inhibitor
BCL-2 inhibitor
Additional relevant MeSH terms:
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Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents