Back to resultsCYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS
Primary Purpose
AML, MDS
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CYC065
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for AML focused on measuring CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia, myelodysplastic syndromes, AML, MDS
Eligibility 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
Sites / Locations
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CYC065 and venetoclax
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximum tolerated dose (MTD)
Number of patients who experience dose-limiting toxicity (DLT)
Secondary Outcome Measures
Pharmacokinetic effect
plasma drug level
Pharmacodynamic effect
MCL-1 level in peripheral white blood cells
Full Information
NCT ID
NCT04017546
First Posted
July 8, 2019
Last Updated
April 22, 2022
Sponsor
Cyclacel Pharmaceuticals, Inc.
Collaborators
M.D. Anderson Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04017546
Brief Title
CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS
Official Title
A Phase I Combination Study of CYC065 and Venetoclax in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2, 2019 (Actual)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cyclacel Pharmaceuticals, Inc.
Collaborators
M.D. Anderson Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AML, MDS
Keywords
CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia, myelodysplastic syndromes, AML, MDS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CYC065 and venetoclax
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CYC065
Intervention Description
intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
oral capsule
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
Number of patients who experience dose-limiting toxicity (DLT)
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Pharmacokinetic effect
Description
plasma drug level
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Title
Pharmacodynamic effect
Description
MCL-1 level in peripheral white blood cells
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Other Pre-specified Outcome Measures:
Title
Anti-tumor activity
Description
Number of patients achieving complete remission, partial remission, hematological improvement as evaluated using International Working Group (IWG) response criteria
Time Frame
from the date of first dose of CYC065 to 4 weeks after the last dose of CYC065
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gautam Borthakur, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32645016
Citation
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.
Results Reference
derived
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CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS
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