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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CTX-712
Sponsored by
Chordia Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria: Age ≥18 years. Diagnosis of AML, HR-MDS, or high marrow blast MDS/MPN (including CMML). Prior treatment history must include 1-4 prior lines of therapy. 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. Exclusion criteria: 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. History of or chimeric antigen receptor T-cell therapy or other modified T cell therapy. 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. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Sites / Locations

  • Mayo Clinic ArizonaRecruiting
  • Mayo Clinic FloridaRecruiting
  • Mayo Clinic Comprehensive Cancer CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Escalation Cohort

Dose Expansion Cohort

Phase 2

Arm Description

Drug: CTX-712 administered at 20 mg, 40 mg, 80 mg, 100 mg, 140 mg weekly

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

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

Outcomes

Primary Outcome Measures

Phase 1: Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to CTX-712.
Phase 1: The maximum tolerated dose MTD.
MTD is the dose producing <33% of dose-limiting toxicities.
Phase 2: Complete remission rate, defined as the proportion of patients who achieve complete remission.

Secondary Outcome Measures

Phase 1 and 2: Objective response rate, defined as the proportion of patients achieving a response.
For AML: CR, CRi, PR, MLFS. For MDS: CR, PR, mCR, HI.
Phase 1 and 2: Duration of response.
Phase 1 and 2: Progression-free survival.
Phase 1 and 2: Overall survival.
Phase 1 and 2: Proportion of patients who transition to hematopoietic stem cell transplantation (HSCT).
Phase 1: Maximum observed plasma concentration (Cmax) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
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.
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.
Phase 1: Volume of distribution (Vd) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
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.
Phase 1: Clearance (CL) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
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.

Full Information

First Posted
January 24, 2023
Last Updated
July 19, 2023
Sponsor
Chordia Therapeutics, Inc.
Collaborators
Theradex
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1. Study Identification

Unique Protocol Identification Number
NCT05732103
Brief Title
A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
Official Title
Phase 1/2 Multicenter, Open-Label Study of CTX-712 in Patients With Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 25, 2023 (Actual)
Primary Completion Date
April 2026 (Anticipated)
Study Completion Date
April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chordia Therapeutics, Inc.
Collaborators
Theradex

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Cohort
Arm Type
Experimental
Arm Description
Drug: CTX-712 administered at 20 mg, 40 mg, 80 mg, 100 mg, 140 mg weekly
Arm Title
Dose Expansion Cohort
Arm Type
Experimental
Arm Description
Drug: CTX-712 administered at a dose to be determined from the data of dose escalation cohort
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
CTX-712 administered at the recommended dose by the expansion cohort
Intervention Type
Drug
Intervention Name(s)
CTX-712
Intervention Description
CTX-712 will be provided as a 20 mg tablet for oral administration. Patients will take CTX-712 weekly, depending on their dose level assignment, during each 28-day cycle.
Primary Outcome Measure Information:
Title
Phase 1: Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to CTX-712.
Time Frame
Adverse events are collected from time of informed consent through 28 days after last dose of CTX-712.
Title
Phase 1: The maximum tolerated dose MTD.
Description
MTD is the dose producing <33% of dose-limiting toxicities.
Time Frame
Dose-limiting toxicities are collected during the first treatment cycle (28 days).
Title
Phase 2: Complete remission rate, defined as the proportion of patients who achieve complete remission.
Time Frame
Measured from date of first dose to 28 days after last dose of CTX-712.
Secondary Outcome Measure Information:
Title
Phase 1 and 2: Objective response rate, defined as the proportion of patients achieving a response.
Description
For AML: CR, CRi, PR, MLFS. For MDS: CR, PR, mCR, HI.
Time Frame
Measured from date of first dose to 28 days after last dose of CTX-712.
Title
Phase 1 and 2: Duration of response.
Time Frame
Measure from documentation of tumor response to disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Title
Phase 1 and 2: Progression-free survival.
Time Frame
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.
Title
Phase 1 and 2: Overall survival.
Time Frame
Measured from the date of initiating study treatment to the date of death from any cause, assessed up to 36 months.
Title
Phase 1 and 2: Proportion of patients who transition to hematopoietic stem cell transplantation (HSCT).
Time Frame
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.
Title
Phase 1: Maximum observed plasma concentration (Cmax) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).
Title
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.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycles 1, 2 and 4 (cycle duration is 28 days).
Title
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.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).
Title
Phase 1: Volume of distribution (Vd) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).
Title
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.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).
Title
Phase 1: Clearance (CL) of CTX-712. Plasma samples for PK analyses will be collected at predetermined time points and analyzed.
Time Frame
Pharmacokinetic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).
Title
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.
Time Frame
Pharmacodynamic evaluation performed in treatment Cycle 1 (cycle duration is 28 days).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Age ≥18 years. Diagnosis of AML, HR-MDS, or high marrow blast MDS/MPN (including CMML). Prior treatment history must include 1-4 prior lines of therapy. 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. Exclusion criteria: 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. History of or chimeric antigen receptor T-cell therapy or other modified T cell therapy. 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. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laurie F Graham, RN, MSN
Phone
(609) 608-2152
Email
lgraham@theradex.com
First Name & Middle Initial & Last Name or Official Title & Degree
Haris Durutlic
Phone
(781) 560-4419
Email
hdurutlic.chordia@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
First Name & Middle Initial & Last Name & Degree
Cecilia A Yi, MD, MSHS
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
First Name & Middle Initial & Last Name & Degree
James Foran, MD
Facility Name
Mayo Clinic Comprehensive Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
First Name & Middle Initial & Last Name & Degree
Antoine Saliba, MD
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristy Bodden
Phone
713-563-4412
Email
krbodden@mdanderson.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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