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

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ClinicalTrials.gov Identifier: NCT04017546
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Cyclacel Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
AML MDS Drug: CYC065 Drug: Venetoclax Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Combination Study of CYC065 and Venetoclax in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
Estimated Study Start Date : July 17, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: CYC065 and venetoclax
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
intravenous infusion

Drug: Venetoclax
oral capsule




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    Number of patients who experience dose-limiting toxicity (DLT)


Secondary Outcome Measures :
  1. Pharmacokinetic effect [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    plasma drug level

  2. Pharmacodynamic effect [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    MCL-1 level in peripheral white blood cells


Other Outcome Measures:
  1. Anti-tumor activity [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04017546


Contacts
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Contact: Judy Chiao, MD 9085177330 jchiao@cyclacel.com

Locations
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United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Hind Alazzawi    713-794-4823    halazzawi@mdanderson.org   
Principal Investigator: Gautam Borthakur, MD         
Sponsors and Collaborators
Cyclacel Pharmaceuticals, Inc.
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Gautam Borthakur, MD M.D. Anderson Cancer Center

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Responsible Party: Cyclacel Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04017546     History of Changes
Other Study ID Numbers: CYC065-03
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cyclacel Pharmaceuticals, Inc.:
venetoclax
acute myeloid leukemia
CYC065
CDK2/9
BCL-2
MCL-1
Relapsed
Refractory
myelodysplastic syndromes
AML
MDS
Additional relevant MeSH terms:
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Venetoclax
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Adenosine
Antineoplastic Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action