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

Sponsor

AbbVie (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02640833

Collaborator

Infinity Pharmaceuticals, Inc. (Industry)

Enrollment

Locations

Arm

55.1

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

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 :

Jul 1, 2016

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Feb 1, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events [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 [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 [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 [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 [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 [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 [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 [Minimum first cycle of dosing (28 days)]
Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib [Minimum first cycle of dosing (28 days)]

Secondary Outcome Measures

Progression-free survival (PFS) [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) [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) [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) [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 145677	Tucson	Arizona	United States	85724-5024
2	Site Reference ID/Investigator# 147922	Chicago	Illinois	United States	60611
3	Site Reference ID/Investigator# 148562	Harvey	Illinois	United States	60426
4	Site Reference ID/Investigator# 148561	Goshen	Indiana	United States	46526
5	Site Reference ID/Investigator# 145674	Baltimore	Maryland	United States	21287
6	Site Reference ID/Investigator# 145145	Boston	Massachusetts	United States	02215
7	Site Reference ID/Investigator# 148010	Detroit	Michigan	United States	48202
8	Site Reference ID/Investigator# 147747	St. Louis	Missouri	United States	63110
9	Site Reference ID/Investigator# 145146	Lebanon	New Hampshire	United States	03756
10	Site Reference ID/Investigator# 148559	Greenville	South Carolina	United States	29605