Relapsed or Refractory Chronic Lymphocytic Leukemia
Conditions
Keywords
CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, chronic lymphocytic leukemia, small lymphocytic lymphoma
Brief summary
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Detailed description
This is an open-label, single arm, dose escalation study in patients with relapsed or refractory CLL. Treatment will be administered on an outpatient basis and all patients will receive CYC065 over 4-hour infusion once every 2 weeks on Day 1 and Day 15 in combination with venetoclax. One treatment cycle is 4 weeks.
Interventions
DRUGCYC065
intravenous infusion
DRUGVenetoclax
oral capsule
Sponsors
Cyclacel Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Three to 6 patients will be entered at a given CYC065 dose level. Dose escalation will be 33% until one out of 3 patients experienced a DLT at a given dose level. Dose escalation will continue at 25% if no additional DLT is observed; otherwise, dose escalation will be stopped. At least 6 patients will be treated at RD.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CLL that is relapsed or refractory to BTK inhibitors and is on a stable dose of venetoclax * ECOG 0-2 * Adequate bone marrow function * Adequate renal function * Adequate liver function * INR \<=1.2 in patients not receiving chronic anticoagulation * At least 4 weeks from prior cytotoxic chemotherapy * At least 4 weeks from major surgery * Agree to practice effective contraception
Exclusion criteria
* Known CLL involvement in CNS that is symptomatic and active * currently receiving radiotherapy, biological therapy, or any other investigational agents * Uncontrolled intercurrent illness * Pregnant or lactating * Known to be HIV-positive * Known active hepatitis B and/or hepatitis C infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients who experience dose-limiting toxicity (DLT) | At the end of cycle 1 (each cycle is 28 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic effect | At the end of cycle 1 (each cycle is 28 days) | Plasma drug level |
| Pharmacodynamic effect | At the end of cycle 1 (each cycle is 28 days) | MCL-1 level in peripheral white blood cells |
Other
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor activity | From the date of first dose of CYC065 to 4 weeks after the last dose of CYC065 | Response assessed by investigators based on International Workshop for CLL criteria or International Working Group criteria for patients with small lymphocytic lymphoma. |
Countries
United States
Outcome results
None listed