Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

NCT ID: NCT04501939

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-06
• Study Completion Date: 2026-07-22

Brief Summary

Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab consolidation in patients with measurable disease on venetoclax.

Detailed Description

This is a phase 2 study to test whether cirmtuzumab in combination with venetoclax given as consolidation therapy can decrease the number of cancer cells that may be left in the bone marrow or in the blood in patients who have been treated with venetoclax for at least one year. Consolidation therapy is given after initial cancer treatment to further reduce the number of cancer cells that may be left in the body. Cirmtuzumab, a monoclonal antibody that inhibits receptor tyrosine kinase like orphan receptor (ROR1) signaling and stemness, may be effective in reducing the risk of disease progression in patients with detectable minimal residual disease (MRD) after treatment with venetoclax.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cirmtuzumab + Venetoclax

All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.

Group Type: EXPERIMENTAL

Cirmtuzumab

Intervention Type: DRUG

Cycle 1, Day 1 \& 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg

Venetoclax

Intervention Type: DRUG

Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.

Interventions

Cirmtuzumab

Cycle 1, Day 1 \& 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg

Intervention Type: DRUG

Venetoclax

Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.

Intervention Type: DRUG

Other Intervention Names

Zilovertamab; VENCLEXTA

Eligibility Criteria

Inclusion Criteria

• Must have detectable CLL/SLL (> 0.01% leukemia cells present)
• Must have received at least 12 months of venetoclax.
• Patients may be receiving venetoclax at the time of screening and study entry.
• Patients who have discontinued venetoclax more than 6 months prior to study entry must still have a disease burden meeting criteria for low risk of TLS (i.e. no lymph node greater than 5 cm in diameter; absolute lymphocyte count less than 25 k/uL)

Exclusion Criteria

Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
• Child class B or C cirrhosis

Treatment with any of the following within 7 days prior to the first dose of cirmtuzumab:

• Steroid therapy for anti-neoplastic intent
• Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent.
• Chemotherapy (purine analog or alkylating agent) or target small molecule agent within 14 days or 5 half-lives (whichever is shorter), or has not recovered to less than CTCAE grade 2 clinically significant adverse effect(s)/toxicity(s) of previous therapy.
• CLL therapy, aside from venetoclax.
• History of other malignancy that could affect compliance with the protocol or interpretation of results (example: patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible.)
• Women who are pregnant or lactating

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oncternal Therapeutics, Inc

INDUSTRY

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Michael Choi

Associate Clin Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benjamin M Heyman, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

UCSD Koman Family Outpatient Pavilion

San Diego, California, United States

Countries

United States

References

Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.

Reference Type: DERIVED

PMID: 34398557 (View on PubMed)

Other Identifiers

191407

Identifier Type: -

Identifier Source: org_study_id