Chronic Lymphocytic Leukemia
Conditions
Keywords
chronic lymphocytic leukemia, CLL, cirmtuzumab, venetoclax
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.
Interventions
DRUGCirmtuzumab
Cycle 1, Day 1 & 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg
DRUGVenetoclax
Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.
Sponsors
Oncternal Therapeutics, Inc
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cancer response to treatment | 6-24 months | Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in gene expression in leukemic cells | 9-15 months | 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. |
Countries
United States
Outcome results
None listed