Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS

NCT03534323 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 18-089
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is assessing a new drug, duvelisib, in combination with a drug that is already FDA approved, venetoclax, as a possible treatment for participants with CLL or those with Richter's Syndrome

Conditions

Chronic Lymphocytic Leukemia; Richter Syndrome

Keywords

chronic lymphocytic leukemia (CLL); Richter's Syndrome; Richter's Transformation

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate (CRR)

  The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) based on IWCLL 2008 and Lugano 2014 criteria for RS.

  Response assessment on the end of cycle 3, 6 and 13. With 28 days per cycle.

• Overall Response Rate (ORR)

  The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on IWCLL 2008 and Lugano 2014 criteria for RS.

  Response assessment on the end of cycle 3, 6 and 13. With 28 days per cycle.

Secondary Outcomes (3)

• 12-month Progression-Free Survival (PFS) Rate

  Relevant to this endpoint is at 12 month.

• 1-year Overall Survival (OS)

  Relevant to this endpoint is 1 year.

• 1-year MRD Negativity Rate

  At 1 year

Study Arms (4)

Phase 1 Level 1: 100 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

EXPERIMENTAL

Duvelisib will be given alone for the first seven days. On day 8 Venetoclax will be added. * Duvelisib will be administered orally twice daily of 25mg * Venetoclax will be administered orally daily of 100mg * All patients will be admitted for administration of the initial dose of venetoclax at each dose escalation

Drug: Duvelisib; Drug: Venetoclax

Phase 1 Level 2: 200 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

EXPERIMENTAL

* Duvelisib will be administered orally twice daily of 25mg * Venetoclax will be administered orally daily of 200mg * All patients will be admitted for administration of the initial dose of venetoclax at each dose escalation

Drug: Duvelisib; Drug: Venetoclax

Phase 1 Level 3: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

EXPERIMENTAL

* Duvelisib will be administered orally twice daily of 25mg * Venetoclax will be administered orally daily of 400mg * All patients will be admitted for administration of the initial dose of venetoclax at each dose escalation

Drug: Duvelisib; Drug: Venetoclax

Phase 2: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

EXPERIMENTAL

* Duvelisib will be administered orally twice daily of 25mg * Venetoclax will be administered orally daily of 400mg

Drug: Duvelisib; Drug: Venetoclax

Interventions

Duvelisib DRUG

This drug is designed to stop cancer growth by blocking a protein called phosphatidylinositide 3-kinase (PI3K), which is important for the survival of CLL cells.

Also known as: IPI-145

Phase 1 Level 1: 100 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 1 Level 2: 200 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 1 Level 3: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 2: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

Venetoclax DRUG

Venetoclax targets a protein called BCL-2, which helps cancer cells survive.

Also known as: Venclexta

Phase 1 Level 1: 100 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 1 Level 2: 200 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 1 Level 3: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID); Phase 2: 400 mg Venetoclax (daily) + 25 mg Duvelisib (BID)

Eligibility Criteria

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

You may qualify if:

• Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma requiring therapy, as per IW-CLL 2008 criteria OR Biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome
• Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy - If Richter's Syndrome, this criterion is not applicable
• Age greater to or equal to 18 years
• ECOG performance status ≤2 (Karnofsky ≥60%)
• Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of CLL confirmed on biopsy:
• Absolute neutrophil count ≥500 cells/mm3 (0.5 x 109/L). Growth factor is allowed in order to achieve this
• Platelet count ≥25,000 cells/mm3 (25 x 109/L) independent of transfusion within 7 days of screening
• Adequate hepatic function defined as:
• 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 as:
• Serum creatinine ≤1.5 times the upper limit of normal or creatinine clearance ≥ 50 mL/min using a 24-hour urine collection
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method or abstinence) prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Previous treatment with venetoclax or duvelisib
• 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
• Confirmed central nervous system involvement
• Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis
• History of active malignancy requiring therapy with the exception of hormonal therapy
• Any active systemic infection requiring IV antibiotics or uncontrolled, active infections
• Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
• Major surgery within 4 weeks of first dose of study drug
• Currently active gastrointestinal disease, including colitis, inflammatory bowel disease and diarrhea requiring therapy
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
• Use of Coumadin for anticoagulation (other anticoagulants permitted)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Secura Bio, Inc.: collaborator

Study Sites (7)

University of Miami- Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Northern Light Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Berkshire Medical Center

Pittsfield, Massachusetts, 01201, United States

Location

Related Publications (1)

• Crombie JL, Ryan CE, Ren Y, Tyekucheva S, Carey C, Zou A, Normilus S, Montegaard J, Bhandari S, Alencar AJ, Soumerai JD, Arnason JE, Kim AI, Parry EM, Armand P, Fisher DC, Brown JR, Davids MS. A phase I/II Study of Duvelisib plus Venetoclax in Patients with Relapsed/Refractory CLL/SLL or Richter Transformation. Blood Adv. 2026 Mar 26:bloodadvances.2025018878. doi: 10.1182/bloodadvances.2025018878. Online ahead of print.

  PMID: 41886642 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

duvelisib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; 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

Results Point of Contact

• Title: Matthew Davids, MD, MMSc - Principal Investigator
• Organization: Dana-Farber Cancer Institute

matthew_davids@dfci.harvard.edu

617-632-6331

Study Officials

• Matthew S Davids, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 23, 2018
• Study Start: July 12, 2018
• Primary Completion: December 1, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 23, 2026
• Results First Posted: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)