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

NCT04017546 | Completed Phase 1 FDA Drug

• 1 other identifier: CYC065-03
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

AML; MDS

Keywords

CYC065; CDK2/9; venetoclax; BCL-2; MCL-1; Relapsed; Refractory; acute myeloid leukemia; myelodysplastic syndromes; AML; MDS

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Number of patients who experience dose-limiting toxicity (DLT)

  At the end of cycle 1 (each cycle is 28 days)

Secondary Outcomes (2)

• Pharmacokinetic effect

  At the end of cycle 1 (each cycle is 28 days)

• Pharmacodynamic effect

  At the end of cycle 1 (each cycle is 28 days)

Other Outcomes (1)

• Anti-tumor activity

  from the date of first dose of CYC065 to 4 weeks after the last dose of CYC065

Study Arms (1)

CYC065 and venetoclax

EXPERIMENTAL

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; Drug: Venetoclax

Interventions

CYC065 DRUG

intravenous infusion

CYC065 and venetoclax

Venetoclax DRUG

oral capsule

CYC065 and venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cyclacel Pharmaceuticals, Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 32645016 DERIVED

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

CYC065; venetoclax

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Gautam Borthakur, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 12, 2019
• Study Start: August 2, 2019
• Primary Completion: November 15, 2022
• Study Completion: April 5, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)