Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

Phase 2

Active, not recruiting

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Cirmtuzumab; Drug: Venetoclax

• Registration Number: NCT04501939
• Lead Sponsor: University of California, San Diego

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.

Study Timeline

• Study First Submitted: 2020-07-22
• Study First Submitted QC: 2020-08-03
• Study Start: 2020-08-06
• Study First Posted: 2020-08-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-27
• Last Update Posted: 2023-11-28
• Primary Completion: 2025-07-22
• Study Completion: 2025-07-22

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cirmtuzumab + Venetoclax	Cirmtuzumab	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.
Cirmtuzumab + Venetoclax	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.

Primary Outcome Measures

Name	Time	Method
Cancer response to treatment	6-24 months	Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.

Secondary Outcome Measures

Name	Time	Method
Frequency of adverse events	9-15 months	Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
Time to next CLL treatment.	9-24 months	Measurement of time of anti-cancer activity

Trial Locations

Locations (1)

UCSD Koman Family Outpatient Pavilion; 🇺🇸 San Diego, California, United States