A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
- Conditions
- Acute Myeloid LeukemiaMyelodysplastic Syndromes
- Interventions
- Registration Number
- NCT05732103
- Lead Sponsor
- Chordia Therapeutics, Inc.
- Brief Summary
The goal of this phase 1/2 multicenter, open-label, singe arm dose escalation and expansion study is to assess the safety, tolerability, pharmacokinetic and pharmacodynamic profile of CTX-712 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and higher risk myelodysplastic syndromes (HR-MDS).
The phase 1 part of the study consists of sequential standard 3 + 3 dose escalation, where patients will receive ascending doses of CTX-712 to determine the recommended phase 2 dose (RP2D) for further clinical development. This is followed by a confirmatory phase 1 expansion cohort where an additional approximately 10 patients will be treated with CTX-712 at the RP2D to gain further confidence in the selected dose level. After RP2D is determined, Drug-Drug-Interaction cohorts will be started.
The phase 2 part of the study will commence after the RP2D has been identified and confirmed and will evaluate therapeutic activity in R/R AML or R/R HR-MDS, in addition to confirmation of the safety profile.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Cohort CTX-712 Drug: CTX-712 administered at 20 mg, 40 mg, 80 mg, 100 mg, 140 mg weekly Phase 2 CTX-712 CTX-712 administered at the recommended dose by the expansion cohort Dose Expansion Cohort CTX-712 Drug: CTX-712 administered at a dose to be determined from the data of dose escalation cohort
- Primary Outcome Measures
Name Time Method Phase 1: Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to CTX-712. Adverse events are collected from time of informed consent through 28 days after last dose of CTX-712. Phase 2: Complete remission rate, defined as the proportion of patients who achieve complete remission. Measured from date of first dose to 28 days after last dose of CTX-712. Phase 1: The maximum tolerated dose MTD. Dose-limiting toxicities are collected during the first treatment cycle (28 days). MTD is the dose producing \<33% of dose-limiting toxicities.
- Secondary Outcome Measures
Name Time Method Phase 1: Elimination half-life of plasma concentration of CTX-712 at terminal phase (T1/2). Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1: Measurement of the change in RNA splicing by CTX-712 in peripheral blood samples as pharmacodynamic markers. Peripheral blood samples for PD analyses will be collected at predetermined time points and analyzed. Pharmacodynamic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1 and 2: Objective response rate, defined as the proportion of patients achieving a response. Measured from date of first dose to 28 days after last dose of CTX-712. For AML: CR, CRi, PR, MLFS. For MDS: CR, PR, mCR, HI.
Phase 1 and 2: Duration of response. Measure from documentation of tumor response to disease progression or death from any cause, whichever occurs first, assessed up to 24 months. Phase 1 and 2: Proportion of patients who transition to hematopoietic stem cell transplantation (HSCT). Measured from the date of the last administration of CTX-712 until HSCT, or one year from the date of the start of administration of CTX-712. Phase 1: Clearance (CL) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1 and 2: Progression-free survival. Measured from the date of initiating study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to 24 months. Phase 1 and 2: Overall survival. Measured from the date of initiating study treatment to the date of death from any cause, assessed up to 36 months. Phase 1: Maximum observed plasma concentration (Cmax) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1: Area under the plasma concentration time curve (AUC) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1: Volume of distribution (Vd) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days). Phase 1: Concentration before dose at steady state (Ctrough) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed. Pharmacokinetic evaluation performed in treatment Cycles 1, 2 and 4 (cycle duration is 28 days).
Trial Locations
- Locations (4)
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Comprehensive Cancer Center
🇺🇸Rochester, Minnesota, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States