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出境医 / 临床实验 / CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS

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

Study Description
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
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
Arms and Interventions
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
Outcome Measures
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


Eligibility 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
Contacts and Locations

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
Tracking Information
First Submitted Date  ICMJE July 8, 2019
First Posted Date  ICMJE July 12, 2019
Last Update Posted Date July 12, 2019
Estimated Study Start Date  ICMJE July 17, 2019
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019) 		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)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • Pharmacokinetic effect [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    plasma drug level
  • Pharmacodynamic effect [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    MCL-1 level in peripheral white blood cells
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 11, 2019) 		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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS
Official Title  ICMJE A Phase I Combination Study of CYC065 and Venetoclax in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE
  • AML
  • MDS
Intervention  ICMJE
  • Drug: CYC065
    intravenous infusion
  • Drug: Venetoclax
    oral capsule
Study Arms  ICMJE 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.
Interventions:
  • Drug: CYC065
  • Drug: Venetoclax
Publications * Frame S, Saladino C, MacKay C, Atrash B, Sheldrake P, McDonald E, Clarke PA, Workman P, Blake D, Zheleva D. Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer. PLoS One. 2020 Jul 9;15(7):e0234103. doi: 10.1371/journal.pone.0234103. eCollection 2020. Erratum in: PLoS One. 2021 May 6;16(5):e0251671.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2019) 		25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Judy Chiao, MD 9085177330 jchiao@cyclacel.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04017546
Other Study ID Numbers  ICMJE CYC065-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cyclacel Pharmaceuticals, Inc.
Study Sponsor  ICMJE Cyclacel Pharmaceuticals, Inc.
Collaborators  ICMJE M.D. Anderson Cancer Center
Investigators  ICMJE
Principal Investigator: Gautam Borthakur, MD M.D. Anderson Cancer Center
PRS Account Cyclacel Pharmaceuticals, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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