CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS

Study Overview
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Brief Summary
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A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory AML or MDS

Detailed Description
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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.

Official Title
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A Phase I Combination Study of CYC065 and Venetoclax in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

Conditions
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AML, MDS

Intervention / Treatment
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* Drug: CYC065
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYC065 and venetoclax<br>CYC065 will be administered intravenously via 4-hour infusion on Day 1 and Day 15. Venetoclax will be taken daily on Day 1 through Day 15. One cycle will be 28 days or 4 weeks. | Drug: CYC065<br>* intravenous infusion<br>Drug: Venetoclax<br>* oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Number of patients who experience dose-limiting toxicity (DLT) | At the end of cycle 1 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic effect | plasma drug level | At the end of cycle 1 (each cycle is 28 days) | 
| Pharmacodynamic effect | MCL-1 level in peripheral white blood cells | At the end of cycle 1 (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia, myelodysplastic syndromes, AML, MDS