Clinical trial NCT04501939: Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax
Official title: Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: chronic lymphocytic leukemia
CLL
cirmtuzumab
venetoclax
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Oncternal Therapeutics, Inc
First posted: 2020-08-06
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cancer response to treatment
timeFrame: 6-24 months
Secondary outcomes:
measure: Frequency of adverse events
timeFrame: 9-15 months
measure: Time to next CLL treatment.
timeFrame: 9-24 months
Other outcomes:
measure: Change in gene expression in leukemic cells
timeFrame: 9-15 months
Locations:
city: San Diego
country: United States
facility: UCSD Koman Family Outpatient Pavilion
state: California
Study officials:
affiliation: University of California, San Diego
name: Benjamin M Heyman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.