A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS

Study Overview
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Brief Summary
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A Phase I Pharmacologic Study of CYC140, a polo-like kinase 1 inhibitor, in Patients with Advanced Leukemias or Myelodysplastic Syndromes

Detailed Description
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This is a First in Human, open-label, single arm, dose escalation study in patients with advanced leukemias or myelodysplastic syndromes. Patients will receive CYC140 as a 1 hr infusion once a week for 2 weeks followed by 1 week of rest on an outpatient basis. One treatment cycle is 3 weeks.

Official Title
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A Phase I Pharmacologic Study of CYC140, a Polo-like Kinase 1 Inhibitor, in Patients With Advanced Leukemias or Myelodysplastic Syndromes

Conditions
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AML, Adult, Myelodysplastic Syndromes, ALL, Adult, CML, Refractory, CLL, Refractory

Intervention / Treatment
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* Drug: CYC140


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of relapsed or refractory advanced leukemias or MDS ECOG 0-2 Adequate renal function Adequate liver function ≥ 2 weeks from prior chemotherapy, radiation therapy or major surgery ≥ 4 weeks from other investigational anticancer therapy Agree to practice effective contraception Exclusion Criteria: Known CNS involvement by leukemia 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 three patients will be entered at a given dose level of CYC140. During the first cycle, all patients will be evaluated for DLTs. If DLT occurs, additional patients (up to 3) will be dosed at that dose. If no additional DLTs observed, dose escalation will continue per protocol. If a DLT does occur, dose escalation will be stopped. At least 6 patients will be treated at the RD to confirm its tolerability.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYC140 single agent<br>CYC140 will be administered as a single agent on Day 1 and Day 8 of each 3 week cycle | Drug: CYC140<br>* CYC140 single agent<br>|

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 end of cycle 1 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic measurement - area under the curve (AUC) | plasma drug exposure area under the curve (AUC) | At the end of cycle 1 (each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, ALL, CLL, CML, MDS, advanced leukemias, leukemia