AML, MDS
Conditions
Keywords
CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia, myelodysplastic syndromes, AML, MDS
Brief summary
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory AML or MDS
Detailed description
This is an open-label, single arm, dose escalation study in patients with relapsed or refractory AML or MDS. 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
One to 6 patients will be entered at a given CYC065 dose level. Dose escalation will be 33% after at least one patient has completed the first treatment cycle without ≥ grade 2 toxicity considered by the investigator to be related to CYC065. Upon the first occurrence of grade 2 toxicity related to CYC065, at least 3 patients will be entered at each dose level. If no DLT is observed in any patients, dose escalation will continue to be 33%. If one of 3 patients experienced a DLT at a given dose level, dose escalation will continue at 25% until MTD is reached. If 2 or more patients experienced a DLT at a given dose level, dose escalation will be stopped. At least 6 patients will be treated at MTD.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously treated AML or MDS based on WHO classification and having at least 10% blasts in peripheral blood * ECOG 0-2 * Adequate renal function * Adequate liver function * INR \<=1.2 in patients not receiving chronic anticoagulation * At least 2 weeks from prior cytotoxic chemotherapy, radiation therapy, major surgery or other investigational cancer therapy * Agree to practice effective contraception
Exclusion criteria
* AML is of the subtype of APL or extramedullary myeloid tumor without bone marrow involvment * Known AML 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 | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | At the end of cycle 1 (each cycle is 28 days) | Number of patients who experience dose-limiting toxicity (DLT) |
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 | Number of patients achieving complete remission, partial remission, hematological improvement as evaluated using International Working Group (IWG) response criteria |
Countries
United States
Outcome results
None listed