A Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL

NCT03467867 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2017-1502
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, multicenter, Phase II study to investigate the efficacy and safety of venetoclax in combination with Rituximab/hyaluronidase human in participants with relapsed or refractory chronic lymphocytic leukemia (CLL).

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Leukemia; Venetoclax; Rituximab; Lymphoid; Lymphoproliferative Disorders; Antineoplastic Agents; Neoplasm

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Percentage of Participants With Best Overall Response (OR)(Defined as Complete Response \[CR\], Initial CR \[CRi\], Nodular Partial Response \[nPR\], PR) as Assessed by Investigator Determined Using iwCLL Guidelines

  Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)

Secondary Outcomes (7)

• Disease Response

  12 weeks after Day 1 of last cycle of combination therapy (approximately 5 years, cycle length= 28 days)

• Duration of Responses (DOR)

  Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)

• Time to Progression (TTP)

  Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)

• Progression-Free Survival (PFS)

  Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]

• Overall Survival (OS)

  Baseline up to death (up to approximately 5 years)

Study Arms (1)

Venetoclax + Rituximab

EXPERIMENTAL

Participants will be initially placed in a venetoclax 5 weeks ramp-up period, and will be administered an initial 20 mg oral tablet dose once daily (QD), incrementing weekly up to a maximum dose of 400 mg. Participants will then continue taking venetoclax 400 mg QD from Week 5 onwards, as directed by the investigator in combination with rituximab 375 mg/m\^2 IV on Day 1 of Cycle 1 followed by 13.4 mL of rituximab SC 1,600 mg/26,800 Units vial (1,600 mg rituximab and 26,800 Units hyaluronidase human) on Day 1 of Cycle 2-6.

Drug: Venetoclax; Drug: Rituximab; Drug: Rituximab/Hyaluronidase Human

Interventions

Venetoclax DRUG

Venetoclax will be administered as described in the reporting arm.

Also known as: GDC-0199, ABT-199

Venetoclax + Rituximab

Rituximab DRUG

Rituximab (IV) will be administered as described in the reporting arm.

Also known as: Rituxan

Venetoclax + Rituximab

Rituximab/Hyaluronidase Human DRUG

Rituximab/Hyaluronidase Human (SC) ill be administered as described in the reporting arm.

Also known as: Rituxan Hycela

Venetoclax + Rituximab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Ability and willingness to comply with the requirements of the study protocol
• Patient must have diagnosis of CLL that meets published 2008 IWCLL NCI-WG criteria.
• Patient must have relapsed/refractory disease with an indication for treatment.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
• Adequate hematologic function (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) defined as follows:
• Hemoglobin (\> / =) 9 g/dL
• Absolute neutrophil count (\> / =) 1.0 x 109/L
• Platelet count (\> / =)75 x 109/L
• Adequate renal function, as indicated by:
• Calculated creatinine clearance ≥ 30 mL/min using 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (eCCR; with the use of ideal body mass \[IBM\] instead of mass)
• Adequate liver function, as indicated by:
• AST or ALT (\< / =) 2.5 x ULN
• Total bilirubin \< 1.5 x ULN (or (\< / =) 3 x ULN for patients with documented Gilbert syndrome)
• Female patients who are not of child-bearing potential and female patients of child-bearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1.

You may not qualify if:

• Known hypersensitivity to any of the study drugs
• Allogeneic stem cell transplant within the past 1 year.
• Richter's transformation confirmed by biopsy
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
• Patients with a malignancy that has been treated with surgery alone with curative intent will be included. Individuals in documented remission without treatment for (\> / =) 2 years prior to enrollment may be included at the discretion of the investigator.
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
• Received the following agents within 7 days prior to the first dose of venetoclax:
• Steroid therapy for anti-neoplastic intent
• Strong and moderate CYP3A inhibitors
• Strong and moderate CYP3A inducers
• Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody

Sponsors & Collaborators

• Georgetown University: lead
• Hackensack Meridian Health: collaborator

Study Sites (2)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia; Lymphoproliferative Disorders; Neoplasms

Interventions

venetoclax; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; 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

• Kieron Dunleavy, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 16, 2018
• Study Start: April 26, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 24, 2025

Record last verified: 2025-12

Locations

US (2)