Testing CTX-712 for patients with relapsed or refractory acute myeloid leukemia and higher risk myelodysplastic syndromes

Phase 1/2 Multicenter, Open-Label Study of CTX-712 in Patients With Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes

This study is testing a new treatment called CTX-712 to see if it can help patients with relapsed or hard-to-treat acute myeloid leukemia and higher risk myelodysplastic syndromes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 225 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chordia Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor
• Locations: 8 sites (Phoenix, Arizona and 7 other locations)
• Trial ID: NCT05732103 on ClinicalTrials.gov

What this trial studies

This is a phase 1/2 multicenter, open-label, single-arm study designed to evaluate the safety, tolerability, and pharmacokinetic and pharmacodynamic profile of CTX-712 in patients with relapsed or refractory acute myeloid leukemia (AML) and higher risk myelodysplastic syndromes (HR-MDS). The study will begin with a dose escalation phase to determine the recommended phase 2 dose (RP2D) of CTX-712, followed by an expansion cohort to further assess this dose. Once the RP2D is established, the phase 2 portion will evaluate the therapeutic activity of CTX-712 in the target patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a diagnosis of relapsed or refractory AML or higher risk MDS who have received 1-4 prior lines of therapy.

Not a fit: Patients with early-stage disease or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of leukemia and myelodysplastic syndromes.

How similar studies have performed: Other studies have shown promise with similar approaches in treating AML and MDS, indicating potential for success in this trial.

Eligibility criteria

Inclusion criteria:

1. Age ≥18 years.
2. 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.
3. Prior treatment history must include 1-4 prior lines of therapy. Note: 1-3 prior lines are allowed for patients in the expansion cohorts.
4. 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
5. Eastern Cooperative Oncology Group performance status ≤2.
6. 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.
7. 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.

Exclusion criteria:

1. Diagnosis of acute promyelocytic leukemia.
2. Isolated extramedullary relapse (phase 2 only).
3. Active central nervous system (CNS) leukemia.
4. History of other malignancy.
5. Any of the following cardiopulmonary abnormalities:

   1. Myocardial infarction within six months prior to registration.
   2. New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction \< 50%.
   3. A history of familial long QT syndrome.
   4. Symptomatic atrial or ventricular arrhythmias not controlled by medications.
   5. 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.
   6. Known moderate to severe and clinically significant chronic obstructive pulmonary disease, interstitial lung disease and/or pulmonary fibrosis (e.g., requiring home oxygen therapy).
6. Pregnancy and/or lactation.
7. Major surgery (excluding placement of vascular access) within 4 weeks prior to first dose of CTX-712.
8. History of allogeneic organ transplantation (excluding cornea).
9. 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.
10. History of or chimeric antigen receptor T-cell therapy or other modified T cell therapy.
11. Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus, or acquired immunodeficiency syndrome related illness. Infections controlled with oral anti-infective agents, including prophylactic treatments, are allowed. Patient must be viral load negative.
12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Where this trial is running

Phoenix, Arizona and 7 other locations

• Mayo Clinic Arizona — Phoenix, Arizona, United States (Recruiting)
• Mayo Clinic Florida — Jacksonville, Florida, United States (Recruiting)
• Northwestern University — Chicago, Illinois, United States (Recruiting)
• Mayo Clinic Comprehensive Cancer Center — Rochester, Minnesota, United States (Recruiting)
• The University of Rochester — Rochester, New York, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University of Virginia — Charlottesville, Virginia, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Guillermo Garcia-Manero, MD — M.D. Anderson Cancer Center
• Study coordinator: Laurie F Graham, RN, MSN

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes