CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory CLL

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 Chronic Lymphocytic Leukemia (CLL)

Detailed Description
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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.

Official Title
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A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Conditions
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Relapsed or Refractory Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: CYC065
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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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

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: 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.
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 after the venetoclax ramp-up schedule is completed. Venetoclax will be taken daily at a dose that is deemed safe and tolerable after the ramp-up schedule. One cycle will be 28 days or 4 weeks. | Drug: CYC065<br>* intravenous infusion<br>Drug: Venetoclax<br>* oral capsule<br>* Other names: ABT-199;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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, chronic lymphocytic leukemia, small lymphocytic lymphoma