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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Recruitment Status : Withdrawn (Study Stopped)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

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Non-Hodgkin Lymphoma Drug: Duvelisib Drug: Venetoclax Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
Experimental: Duvelisib+Venetoclax 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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax [ Time Frame: Minimum first cycle of dosing (28 days) ]
  9. Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib [ Time Frame: Minimum first cycle of dosing (28 days) ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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 ClinicalTrials.gov identifier (NCT number): NCT02640833


Locations
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United States, Arizona
Site Reference ID/Investigator# 145677
Tucson, Arizona, United States, 85724-5024
United States, Illinois
Site Reference ID/Investigator# 147922
Chicago, Illinois, United States, 60611
Site Reference ID/Investigator# 148562
Harvey, Illinois, United States, 60426
United States, Indiana
Site Reference ID/Investigator# 148561
Goshen, Indiana, United States, 46526
United States, Maryland
Site Reference ID/Investigator# 145674
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Site Reference ID/Investigator# 145145
Boston, Massachusetts, United States, 02215
United States, Michigan
Site Reference ID/Investigator# 148010
Detroit, Michigan, United States, 48202
United States, Missouri
Site Reference ID/Investigator# 147747
St. Louis, Missouri, United States, 63110
United States, New Hampshire
Site Reference ID/Investigator# 145146
Lebanon, New Hampshire, United States, 03756
United States, South Carolina
Site Reference ID/Investigator# 148559
Greenville, South Carolina, United States, 29605
Sponsors and Collaborators
AbbVie
Infinity Pharmaceuticals, Inc.
Investigators
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Study Director: John Hayslip, MD AbbVie

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02640833     History of Changes
Other Study ID Numbers: M15-330
2015-003302-16 ( EudraCT Number )
First Posted: December 29, 2015    Key Record Dates
Last Update Posted: July 26, 2016
Last Verified: July 2016

Keywords provided by AbbVie:
Refractory Lymphoma
Relapsed Leukemia

Additional relevant MeSH terms:
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Venetoclax
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents