Duvelisib and Venetoclax in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

NCT06810778 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 24-001373NCI-2025-00574
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase I/II study of duvelisib in combination with Venetoclax for patients with relapsed/refractory NHL. Duvelisib is an FDA approved, marketed product used to treat certain patients with leukemia and lymphoma and Venetoclax, which is approved for treatment of certain patients with acute myeloid leukemia. The combination of these two drugs is experimental. Experimental means that it is not approved by the United States Food and Drug Administration (FDA). The researchers want to find out how safe it is to combine these drugs and how well this combination can work for your cancer.

Conditions

T-cell-prolymphocytic Leukemia; Cutaneous T-Cell Lymphoma Refractory

Keywords

leukemia; refractory; relapsed

Outcome Measures

Primary Outcomes (3)

• Determine the dose limiting toxicities (DLTs), for the combination regimen of duvelisib plus venetoclax for patients with relapsed or refractory PTCL

  Phase I: Will be graded according to the Common Terminology Criteria for Adverse Events version 5.0.

  Up to 21 days

• Determine the Maximum Tolerated Dose MTD)

  Phase I: Will be defined as the highest dose studied for which the observed incidence of DLT is less than 33%. Frequencies of toxicities will be tabulated according to the National Cancer Institute Common Toxicity Criteria.

  Up to 21 days

• Recommended phase II dose (Phase I)

  Phase I

  Up to 21 days

Secondary Outcomes (10)

• Overall response rate

  up to 1 year

• Objective response rate

  Up to 1 year

• Duration of response

  From the date of response to the date of progression of disease, assessed up to 1 year

• Progression free survival

  From start of treatment to the date of progression, death or last follow-up, assessed up to 1 year

• Overall survival

  From the start of treatment to the date of death or last follow-up, assessed up to 1 year

Study Arms (1)

Arm Treatment (Duvelisib and Venetoclax)

EXPERIMENTAL

Phase I: In the phase I study, 2 dose levels of duvelisib (15 and 25 mg BID) and 3 dose levels of venetoclax (200, 400, and 800 mg QD) will be evaluated. Patients will start with 15 mg BID of duvelisib and 200 mg QD of venetoclax. We use a traditional 3 + 3 design to accrue patients to each combination cohort. There are 5 possible dosing combinations to be tested, with up to 18 patients planned to be enrolled. Enrollment may stop early based on DLTs. The DLT assessment window is defined as Day 1-21 of Cycle 1 (21 days). De-escalation will occur if unexpected toxicity is observed and both drugs will be reduced for the next lower dosing cohort. Increasing drug dosing levels will be performed in parallel cohorts, each increasing either venetoclax or duvelisib.

Drug: Duvelisib; Drug: Venetoclax

Interventions

Duvelisib DRUG

15 and 25 mg BID

Arm Treatment (Duvelisib and Venetoclax)

Venetoclax DRUG

200, 400, and 800 mg QD

Arm Treatment (Duvelisib and Venetoclax)

Eligibility Criteria

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

You may qualify if:

• Phase I: Histologically confirmed relapsed/refractory PTCL, except the following lymphoma subtypes: cutaneous T-cell lymphoma (CTCL) and T-cell-prolymphocytic leukemia (TPLL).
• Phase II: same as phase I
• Disease that has progressed during or relapsed after at least two previous therapies.
• ECOG performance status ≤ 2
• Adequate hepatic function defined as:
• o Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN), bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
• Adequate renal function as defined by:
• o Creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection
• Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement confirmed on biopsy:
• Absolute neutrophil count ≥ 1500 cells/mm3 (1.5 x 109/L) or ≥ 1000 cells/mm3 (1.5 x 109/L) with bone marrow involvement. Growth factor use is allowed in order to achieve this
• Platelet count ≥ 50,000 cells/mm3 (50 x 109/L) independent of transfusion within 7 days of screening
• Hemoglobin ≥8 g/dL (without transfusion support.)

You may not qualify if:

• Phase I and Phase II:
• Patients eligible for Hematopoietic stem cell transplantation (HSCT)
• Cutaneous T-cell lymphoma (CTCL) and T-cell-prolymphocytic leukemia (TPLL)
• Suspected and confirmed central nervous system involvement
• Previous treatment with venetoclax or a PI3K inhibitor.
• Active malignancy other than NHL requiring ongoing therapy, with the exception of hormonal therapy (i.e. castration-sensitive prostate cancer stable on testosterone blockade)
• Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, surgery) within 2 weeks of Cycle 1/Day 1 with the following exceptions:
• For patients on targeted therapies, a washout of least five half-lives is required
• Patients who experience clinical deterioration may start therapy after a shorter washout period with prior approval by the PI
• Corticosteroid therapy (prednisone or equivalent \<20 mg daily) is allowed
• Patients with multiple basal cell carcinomas that undergo sequential Moh's excisions with interim observation
• Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis
• o Patients with a history of an allogeneic stem cell transplant \> 6 months prior to starting study treatment should be stable, off of immunosuppression for at least 2 months.
• Any active systemic infection requiring systemic antibiotics or other uncontrolled, active infections
• Positive Human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) antibody test

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

David Geffen School of Medicine at the University of California at Los Angeles

Los Angeles, California, 90095-1406, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Prolymphocytic, T-Cell; Leukemia; Recurrence

Interventions

duvelisib; venetoclax

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Vladimir Bonhomme

CONTACT

310-794-6500; VBonhomme@mednet.ucla.edu

Vanessa Crowell

CONTACT

vcrowell@mednet.ucla.edu

Study Design

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

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: February 6, 2025
• Study Start: May 2, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: July 15, 2025

Record last verified: 2025-07

Locations

US (1)