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

NCT02640833 | Withdrawn Phase 1

• 2 other identifiers: M15-3302015-003302-16
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 10

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Non-Hodgkin Lymphoma

Keywords

Refractory Lymphoma; Relapsed Leukemia

Outcome Measures

Primary Outcomes (9)

• Number of participants with adverse events

  Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.

  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

• Maximum observed plasma concentration (Cmax) of duvelisib

  The highest concentration that a drug achieves in the blood after administration in a dosing interval.

  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.

• Maximum observed plasma concentration (Cmax) of venetoclax

  The highest concentration that a drug achieves in the blood after administration in a dosing interval.

  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.

• Time to maximum observed plasma concentration (Tmax) of duvelisib

  The time at which the maximum plasma concentration (Cmax) is observed.

  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.

• Time to maximum observed plasma concentration (Tmax) of venetoclax

  The time at which the maximum plasma concentration (Cmax) is observed.

  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.

• Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib

  The area under the plasma concentration-time curve over a 12-hour dose interval

  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.

• Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax

  The area under the plasma concentration-time curve over a 24-hour dose interval

  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.

• 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 Outcomes (4)

• Progression-free survival (PFS)

  Measured up to 2 years after the last participant has enrolled in the study

• Overall Response Rate (ORR)

  Measured up to 2 years after the last participant has enrolled in the study

• Time to Tumor Progression (TTP)

  Measured up to 2 years after the last participant has enrolled in the study

• Duration of Response (DOR)

  Measured up to 2 years after the last participant has enrolled in the study

Study Arms (1)

Duvelisib+Venetoclax

EXPERIMENTAL

Drug: Duvelisib; Drug: Venetoclax

Interventions

Duvelisib DRUG

Duvelisib will be taken continuously. This is a defining dose study, therefore the dose of Duvelisib may change.

Duvelisib+Venetoclax

Venetoclax DRUG

Venetoclax will be taken continuously. This is a defining dose study, therefore the dose of Venetoclax will change.

Duvelisib+Venetoclax

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead
• Infinity Pharmaceuticals, Inc.: collaborator

Study Sites (10)

Site Reference ID/Investigator# 145677

Tucson, Arizona, 85724-5024, United States

Location

Site Reference ID/Investigator# 147922

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 148562

Harvey, Illinois, 60426, United States

Location

Site Reference ID/Investigator# 148561

Goshen, Indiana, 46526, United States

Location

Site Reference ID/Investigator# 145674

Baltimore, Maryland, 21287, United States

Location

Site Reference ID/Investigator# 145145

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 148010

Detroit, Michigan, 48202, United States

Location

Site Reference ID/Investigator# 147747

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 145146

Lebanon, New Hampshire, 03756, United States

Location

Site Reference ID/Investigator# 148559

Greenville, South Carolina, 29605, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia

Interventions

duvelisib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• John Hayslip, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 29, 2015
• Study Start: July 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: February 1, 2021
• Last Updated: July 26, 2016

Record last verified: 2016-07

Locations

US (10)