Safe Accelerated Venetoclax Escalation in CLL

NCT04843904 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-415
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is trying to determine which patients with newly diagnosed or relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), as grouped by their risk for tumor lysis syndrome (TLS), are able to safely tolerate an accelerated, daily venetoclax dose ramp-up rather than the standard approved schedule (5-week dose ramp-up). The name of the study drug involved in this study is:

• Venetoclax The following drugs may also be included in some participants treatment regimen:
• Obinutuzumab
• Rituximab

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Highest risk TLS group that can safely tolerate the daily ramp up

  Rates of laboratory and clinical TLS

  3 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  3 months

• Complete response (CR) rate

  3 months

• Progression free survival (PFS)

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

• Overall survival (OS)

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

• Rate of undetectable minimal residual disease (uMRD)

  3 months

Study Arms (1)

Venetoclax

EXPERIMENTAL

Participants will be separated into two cohorts: Cohort A: Patients at low risk for TLS. Cohort B: Patients with both median and high risk for TLS. Five (5) participants from cohort A will be initially enrolled, if these first 5 participants tolerate the accelerated ramp-up, cohorts A and B will enroll simultaneously. All participants will be hospitalized and receive venetoclax daily with accelerated dose increases over 5 days to reach full dose. After reaching full dose, participants will be discharged and continue daily venetoclax at home. Per doctor assessment, some participants may also receive rituximab or obinutuzumab as part of the treatment regimen with venetoclax. Rituximab: Given every 28 days starting on the second study cycle and continuing for up to 6 cycles as per standard of care. Obinutuzumab: Days 1, 2, 8, and 15 of cycle 1 and once every 28 days there after for up to 6 cycles as per standard of care.

Drug: Venetoclax; Drug: Obinutuzumab; Drug: Rituximab

Interventions

Obinutuzumab DRUG

Given as an infusion into the vein (intravenous, IV).

Also known as: Gazyva

Venetoclax

Venetoclax DRUG

Tablet, taken by mouth

Also known as: Venclexta

Venetoclax

Rituximab DRUG

Given as an infusion into the vein (intravenous, IV).

Also known as: Rituxan

Venetoclax

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 per IW-CLL 201814 requiring therapy based on at least one of the following criteria as listed below:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin \<11.0 g/L) and/or thrombocytopenia (platelets \<100 x 109/L)
• Massive (≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly
• Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic
• lymphadenopathy
• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of \<6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months.
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
• Documented constitutional symptoms, defined as 1 or more of the following disease related symptoms or signs: unintentional weight loss \>10% within 6 months prior to screening, significant fatigue (inability to work or perform usual activities), fevers \>100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection, night sweats for more than 1 month prior to screening without evidence of infection
• Both previously untreated and relapsed or refractory patients will be eligible, including those who will be receiving venetoclax as monotherapy or in combination with anti-CD20 monoclonal antibody therapy
• Age greater or equal to 18 years
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of CLL confirmed on biopsy:
• Absolute neutrophil count ≥1000 cells/mm3. 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:

You may not qualify if:

• Treatment with venetoclax within the past 6 months
• Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia)
• 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
• Active malignancy requiring therapy that would interact with venetoclax as per the discretion of the treating investigator
• Any active systemic infection requiring IV antibiotics or other 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, 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 of initial dosing on study
• Use of Coumadin for anticoagulation (other anticoagulants permitted)
• Lactating or pregnant

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; obinutuzumab; Rituximab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jennifer Crombie, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 14, 2021
• Study Start: April 14, 2021
• Primary Completion: June 2, 2025
• Study Completion (Estimated): June 2, 2030
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)