Clinical trial NCT04017546: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: AML
MDS
Keywords: CYC065
CDK2/9
venetoclax
BCL-2
MCL-1
Relapsed
Refractory
acute myeloid leukemia
myelodysplastic syndromes
AML
MDS
Lead sponsor: Cyclacel Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-12
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: At the end of cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Pharmacokinetic effect
timeFrame: At the end of cycle 1 (each cycle is 28 days)
measure: Pharmacodynamic effect
timeFrame: At the end of cycle 1 (each cycle is 28 days)
Other outcomes:
measure: Anti-tumor activity
timeFrame: from the date of first dose of CYC065 to 4 weeks after the last dose of CYC065
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Gautam Borthakur, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.