Clinical trial NCT02640833: 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: 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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Non-Hodgkin Lymphoma
Keywords: Refractory Lymphoma
Relapsed Leukemia
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Infinity Pharmaceuticals, Inc.
First posted: 2015-12-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 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
measure: Maximum observed plasma concentration (Cmax) of duvelisib
timeFrame: 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.
measure: Maximum observed plasma concentration (Cmax) of venetoclax
timeFrame: 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.
measure: Time to maximum observed plasma concentration (Tmax) of duvelisib
timeFrame: 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.
measure: Time to maximum observed plasma concentration (Tmax) of venetoclax
timeFrame: 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.
measure: Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib
timeFrame: 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.
measure: Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
timeFrame: 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.
measure: Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax
timeFrame: Minimum first cycle of dosing (28 days)
measure: Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib
timeFrame: Minimum first cycle of dosing (28 days)
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Measured up to 2 years after the last participant has enrolled in the study
measure: Overall Response Rate (ORR)
timeFrame: Measured up to 2 years after the last participant has enrolled in the study
measure: Time to Tumor Progression (TTP)
timeFrame: Measured up to 2 years after the last participant has enrolled in the study
measure: Duration of Response (DOR)
timeFrame: Measured up to 2 years after the last participant has enrolled in the study
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Site Reference ID/Investigator# 145677
state: Arizona
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 147922
state: Illinois
city: Harvey
country: United States
facility: Site Reference ID/Investigator# 148562
state: Illinois
city: Goshen
country: United States
facility: Site Reference ID/Investigator# 148561
state: Indiana
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 145674
state: Maryland
city: Boston
country: United States
facility: Site Reference ID/Investigator# 145145
state: Massachusetts
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 148010
state: Michigan
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 147747
state: Missouri
city: Lebanon
country: United States
facility: Site Reference ID/Investigator# 145146
state: New Hampshire
city: Greenville
country: United States
facility: Site Reference ID/Investigator# 148559
state: South Carolina
Study officials:
affiliation: AbbVie
name: John Hayslip, MD
role: STUDY_DIRECTOR
References: