Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

Chronic Lymphocytic Leukemia Clinical Trial

— Venetoclax  

Official title:

Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04501939
• Other study ID #: 191407
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 6, 2020
• Est. completion date: July 22, 2025

Study information

• Verified date: November 2023
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: July 22, 2025
• Est. primary completion date: July 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Cirmtuzumab
Cycle 1, Day 1 & 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg
• Venetoclax
Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.

Locations

Country	Name	City	State
United States	UCSD Koman Family Outpatient Pavilion	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Oncternal Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in gene expression in leukemic cells	The change in gene expression of leukemia cells by single cell PCR or RNA after treatment with cirmtuzumab, including analysis of archival pre-venetoclax sample, when available.	9-15 months
Primary	Cancer response to treatment	Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.	6-24 months
Secondary	Frequency of adverse events	Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.	9-15 months
Secondary	Time to next CLL treatment.	Measurement of time of anti-cancer activity	9-24 months