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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Age ≥18 years. 2. Diagnosis of AML, HR-MDS, or high marrow blast MDS/MPN (including CMML). 3. Prior treatment history must include 1-4 prior lines of therapy. 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation Cohort 		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
    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.
Experimental
Initial Expansion Cohort 		Drug: CTX-712 administered at a dose to be determined from the data of dose escalation cohort
  • Drug: CTX-712
    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.
Experimental
Phase 2 		CTX-712 administered at the recommended dose by the expansion cohort
  • Drug: CTX-712
    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.

Recruiting Locations

Mayo Clinic Arizona
Phoenix, Arizona 85054
Contact:
Clinical Trials Referral Office
855-776-0015

Mayo Clinic Florida
Jacksonville, Florida 32224
Contact:
Clinical Trials Referral Office
855-776-0015

Mayo Clinic Comprehensive Cancer Center
Rochester, Minnesota 55905
Contact:
Clinical Trials Referral Office
855-776-0015

The University of Rochester
Rochester, New York 14642
Contact:
Jason Mendler
WCICTOResearch@URMC.Rochester.edu

The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Contact:
Kristy Bodden
713-563-4412
krbodden@mdanderson.org

University of Virginia
Charlottesville, Virginia 22903
Contact:
Avani Hopkins
434-243-8108
DRR3D@uvahealth.org

Fred Hutchinson Cancer Center
Seattle, Washington 98109
Contact:
Issac Miller
206-606-1894
halpern2@uw.edu

More Details

Status
Recruiting
Sponsor
Chordia Therapeutics, Inc.

Study Contact

Laurie F Graham, RN, MSN
(609) 608-2152
lgraham@theradex.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.