A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes

NCT05732103 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: C22-11236CTX-712-CL-02
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 8

Brief Summary

The goal of this phase 1/2 multicenter, open-label, single-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), or MDS/MPN (including CMML). 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 initial expansion cohorts in AML and/or HR-MDS where patients will be treated with CTX-712 at the RP2D to gain further confidence in the selected dose level. Additional expansion cohorts may be initiated if considered necessary. 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• 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 1: The maximum tolerated dose MTD.

  MTD is the dose producing \<33% of dose-limiting toxicities.

  Dose-limiting toxicities are collected during the first treatment cycle (28 days).

• 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.

Secondary Outcomes (12)

• 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.

• 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: 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 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.

Study Arms (3)

Dose Escalation Cohort

EXPERIMENTAL

Drug: CTX-712 administered at 20 mg, 40 mg, 80 mg, 100 mg, 140 mg weekly, or 60 mg, 80 mg, 100 mg twice a week

Drug: CTX-712

Initial Expansion Cohort

EXPERIMENTAL

Drug: CTX-712 administered at a dose to be determined from the data of dose escalation cohort

Drug: CTX-712

Phase 2

EXPERIMENTAL

CTX-712 administered at the recommended dose by the expansion cohort

Drug: CTX-712

Interventions

CTX-712 DRUG

CTX-712 will be provided as a 20 mg tablet for oral administration. Patients will take CTX-712 once or twice weekly, depending on their dose level assignment, during each 28-day cycle.

Dose Escalation Cohort; Initial Expansion Cohort; Phase 2

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Diagnosis of AML, HR-MDS, or high marrow blast MDS/MPN (including CMML). Note: Only patients with AML and HR-MDS are eligible in the expansion cohorts.
• Prior treatment history must include 1-4 prior lines of therapy. Note: 1-3 prior lines are allowed for patients in the expansion cohorts.
• Adequate organ function evidenced by the following laboratory values:
• Creatinine clearance (CL) ≥60 mL/min
• Total serum bilirubin \< 1.5 × upper limit of normal (ULN)
• Alanine aminotransferase (ALT)
• Aspartate aminotransferase(AST) \< 2.5 × ULN
• White blood cell count at the time of the first dose \<10 k/μL
• Eastern Cooperative Oncology Group performance status ≤2.
• Female patients of childbearing potential must have a negative pregnancy test within 7 days before study treatment initiation and if sexually active, agree to use a highly effective form of contraception throughout their participation during study treatment and up to 4 months after the last dose of study drug.
• Male patients with female partners of childbearing potential must, even if surgically sterilized, agree to practice effective barrier contraception during the entire study treatment period and through four months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia.
• Isolated extramedullary relapse (phase 2 only).
• Active central nervous system (CNS) leukemia.
• History of other malignancy.
• Any of the following cardiopulmonary abnormalities:
• Myocardial infarction within six months prior to registration.
• New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction \< 50%.
• A history of familial long QT syndrome.
• Symptomatic atrial or ventricular arrhythmias not controlled by medications.
• QTcF ≥ 470 msec calculated according to institutional guidelines, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor.
• Known moderate to severe and clinically significant chronic obstructive pulmonary disease, interstitial lung disease and/or pulmonary fibrosis (e.g., requiring home oxygen therapy).
• Pregnancy and/or lactation.
• Major surgery (excluding placement of vascular access) within 4 weeks prior to first dose of CTX-712.
• History of allogeneic organ transplantation (excluding cornea).
• History of allogenic hematopoietic stem cell transplantation within 6 months of planned study treatment initiation and/or graft-versus host disease grade ≥ 1 following allogenic hematopoietic stem cell transplantation.

Sponsors & Collaborators

• Chordia Therapeutics, Inc.: lead
• Theradex: collaborator

Study Sites (8)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Mayo Clinic Comprehensive Cancer Center

Rochester, Minnesota, 55905, United States

RECRUITING

The University of Rochester

Rochester, New York, 14642, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• Yokoyama H, Fukuhara N, Ando K, Iida H, Yamauchi T, Fukuhara S, Izutsu K, Tanoue Y, Yamamoto M, Tozaki H, Takahara E, Shoji S, Mizutani A, Morishita D, Oda R, Miyake H, Yamamoto N. Phase 1 study of rogocekib in patients with relapsed or refractory hematologic malignancies. Blood Adv. 2026 Jan 13;10(1):262-272. doi: 10.1182/bloodadvances.2025017601.

  PMID: 41056522 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurie F Graham, RN, MSN

CONTACT

(609) 608-2152; lgraham@theradex.com

Haris Durutlic

CONTACT

(781) 560-4419; hdurutlic.chordia@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2023
• First Posted: February 16, 2023
• Study Start: April 25, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)