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A Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor

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ClinicalTrials.gov Identifier: NCT02640833
Recruitment Status : Withdrawn (Study Stopped)
First Posted : December 29, 2015
Last Update Posted : July 26, 2016
Sponsor:
Collaborator:
Infinity Pharmaceuticals, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE December 23, 2015
First Posted Date  ICMJE December 29, 2015
Last Update Posted Date July 26, 2016
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
  • Number of participants with adverse events [ Time Frame: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose ]
    Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.
  • Maximum observed plasma concentration (Cmax) of duvelisib [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels. ]
    The highest concentration that a drug achieves in the blood after administration in a dosing interval.
  • Maximum observed plasma concentration (Cmax) of venetoclax [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10, 12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels. ]
    The highest concentration that a drug achieves in the blood after administration in a dosing interval.
  • Time to maximum observed plasma concentration (Tmax) of duvelisib [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels. ]
    The time at which the maximum plasma concentration (Cmax) is observed.
  • Time to maximum observed plasma concentration (Tmax) of venetoclax [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels. ]
    The time at which the maximum plasma concentration (Cmax) is observed.
  • Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels. ]
    The area under the plasma concentration-time curve over a 12-hour dose interval
  • Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax [ Time Frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels. ]
    The area under the plasma concentration-time curve over a 24-hour dose interval
  • Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax [ Time Frame: Minimum first cycle of dosing (28 days) ]
  • Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib [ Time Frame: Minimum first cycle of dosing (28 days) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02640833 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
  • Progression-free survival (PFS) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study ]
    Progression-free survival will be defined as the number of days from the date of study drug start to the date of documented disease progression, relapse of death due to any cause whichever occurs first.
  • Overall Response Rate (ORR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study ]
    Overall response rate will be defined as the proportion of participants who achieve a partial remission or better.
  • Time to Tumor Progression (TTP) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study ]
    Time to tumor progression is defined as the number of days from the date of study drug start to the date of the first documented disease progression or relapse.
  • Duration of Response (DOR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study ]
    Duration of response is defined as the number of days from the date of documented first response of partial remission or better to the date of documented disease progression/relapse or death due to the disease whichever occurs first
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
Official Title  ICMJE A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
Brief Summary This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive non-Hodgkin lymphoma, who have not previously received a Bcl-2 or Phosphoinositide 3-kinase (PI3K) inhibitor. The Phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Duvelisib
    Duvelisib will be taken continuously. This is a defining dose study, therefore the dose of Duvelisib may change.
  • Drug: Venetoclax
    Venetoclax will be taken continuously. This is a defining dose study, therefore the dose of Venetoclax will change.
Study Arms  ICMJE Experimental: Duvelisib+Venetoclax
Interventions:
  • Drug: Duvelisib
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: July 22, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: December 23, 2015)
174
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: -

Subject must have either • Relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (for Waves 2 or 3)

  • Subject has evaluable disease and requires treatment in the opinion of the investigator.
  • Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as fludarabine based regimens (F, FC, FR, FCR), alkylator (chlorambucil, bendamustine) based regimens, or Bruton's Tyrosine Kinase inhibitor (Ibrutinib).

Or

• Relapsed or refractory indolent Non-Hodgkin Lymphoma or aggressive Non-Hodgkin Lymphoma (for Waves 1, 2, or 3, unless otherwise indicated)

  • Subject must have histologically documented diagnosis of a Follicular Lymphoma or Marginal Zone Lymphoma.
  • Subject must have histologically documented diagnosis of a Diffuse Large B-cell Lymphoma (excluding Richter's Transformation), Non-cutaneous T-Cell Lymphoma, or Mantle Cell Lymphoma (MCL) (MCL Wave 3 only)
  • Subject has evaluable disease and requires treatment in the opinion of the investigator.
  • Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as R-CHOP, R-CVP, bendamustine, lenalidomide-rituximab, or fludarabine-based regimens.

    • Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
    • Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
    • Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
    • NHL subjects who have a history of an autologous stem cell transplant (e.g., bone marrow) must be > 6 months post-transplant (prior to the first dose of study drug) and must not require any growth factor support.

Exclusion Criteria:

  • Subject has been previously treated with a Bcl-2 or PI3K inhibitor.
  • Subject is a candidate to receive another second-line therapy approved for usage by the local Health Authority.
  • Subject is appropriate for a stem cell transplant or has undergone an allogeneic stem cell transplant.
  • Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

    • Any anti-cancer therapy including chemotherapy or radiotherapy;
    • Investigational therapy, including targeted small molecule agents.
  • Subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic treatment within 30 days prior to first dose of duvelisib or venetoclax.
  • Subject has received live or live attenuated vaccines within 6 weeks prior to first dose of duvelisib or venetoclax.
  • Subject has received the following within 7 days prior to the first dose of duvelisib or venetoclax:

    • Steroid therapy for anti-neoplastic treatment;
    • Strong and Moderate CYP3A inhibitors;
    • Strong and Moderate CYP3A inducers;
    • Chronic immunosuppressants, other than corticosteroids given at daily dose < 20 mg prednisone equivalent for ITP or AIHA.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02640833
Other Study ID Numbers  ICMJE M15-330
2015-003302-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Infinity Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: John Hayslip, MD AbbVie
PRS Account AbbVie
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP