A Phase I/II, Multicenter, First-in-Human, Dose Escalation and Expansion Study Evaluating CHM-029 as Monotherapy in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) With NPM1 Mutations, KMT2A or NUP98 Rearrangements
Study Identifier:
CHM-029-01
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study Summary
To evaluate the safety of CHM-029, an investigational oral medicine, and to evaluate its activity in treating certain types of acute myeloid leukemia (AML) in adults.
Main objective (English)
To assess the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or optimal biological dose (OBD) of CHM-029 monotherapy and in combination with standard of care therapies in participants with relapsed or treatment-refractory or newly diagnosed AML
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Leukemia
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: CHM-029 Dose Escalation
Read More
Drug: CYTARABINE
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- * 18 years old and above * Relapsed or refractory (R/R) acute myeloid leukemia (AML) and has had treatment with any available standard therapies * Positive for NPM1 mutation, or KMT2A or NUP98 rearrangements
- Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the participant prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- ≥18 years of age at the time of obtaining informed consent.
- Morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2022) and fulfills one of the following: For Cohort 1 and Stage 1 (Escalation) of Cohort 2 • which is relapsed (after previously complete remission, CR, CRh, CRi, or [CCI] per European LeukemiaNet (ELN) recommendations. Note: patients should have received an approved targeted therapy, if eligible.OR • refractory (failed to achieve complete remission) to the last treatment. Note: primary refractory participants should have received at least two cycles of treatment including an approved targeted therapy For Stage 2 (Expansion) of Cohort 2 • Previously-untreated AML and ineligible for intensive induction chemotherapy by meeting following criteria: - ≥ 75 years of age - ≥ 18 to 74 years of age and has one or more of the following: • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 • Cardiac history of chronic heart failure requiring treatment or with an ejection fraction of ≤ 50%, or chronic stable angina • Documented pulmonary disease with diffusing capacity of the lungs for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65% • Creatinine clearance ≥ 30 mL/min to < 45 mL/min calculated by the Cockcroft-Gault formula • Moderate hepatic impairment with total bilirubin > 1.5 to < 3 × upper limit of normal (ULN) • Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy For Cohort 3 Previously-untreated AML and eligible for intensive induction chemotherapy
- Positive for NPM1 mutations, or KMT2A or NUP98 rearrangements as determined by a validated test. Note: participants with KMT2A partial tandem duplications or amplifications are not eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 for Cohort 1 and 3, and ECOG performance status ≤ 3 for Cohort 2.
- For participants with relapsed or refractory disease, participant’s interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents, whichever is shorter.
- Suitable for oral administration of study drug.
- Agree to the reproductive requirements
Exclusion criteria
- White blood cell (WBC) count higher than 25,000 u/L that cannot be maintained below threshold with hydroxyurea treatment * Extramedullary only AML * Has current complications related to hematopoietic stem cell transplant (HSCT) * Other cancers that require treatment * Active Hepatitis or HIV infection * Moderate hepatic or renal impairment * Acute promyelocytic leukemia * Baseline prolongation of QT/QTc interval (≥ 470 ms) or additional risk factors for Torsades de Pointes (TdP) * Congestive heart failure NYHA Class 3 or 4 * Central nervous system involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation
- #1 WBC > 25,000/μL. If the WBC can be maintained below the threshold with hydroxyurea, the participant would be eligible.
- #2 Extramedullary only AML.
- #3 Hematopoietic stem cell transplant (HSCT) and has any of the following: a. Clinically significant graft-versus-host disease requiring systemic treatment; b. ≥ Grade 2 persistent non-hematological toxicity related to the transplant.
- #4 Other malignancy that requires treatment.
- #5 Uncontrolled bacterial, viral, or fungal infections at time of enrollment.
- #6 Active Hepatitis B or C infection.
- #7 Seropositive for HIV-1 or -2
- #8 A marked baseline prolongation of QT/QTc interval (triplicate QTcF ≥ 470 ms).
- #9 A history of additional risk factors for TdP (e.g., heart failure, hypokalemia (resistant to replacement), family history of Long QT syndrome).
- #18 For Cohort 2, Stage 2 only IDH1 mutation eligible for an approved IDH1 inhibitor in combination with azacitidine treatment
- #10 CNS involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation.
- #11 AST or ALT > 3 × upper limit of normal ULN
- #12 Acute promyelocytic leukemia.
- #13 Any condition, in the judgement of the Investigator, that would interfere with study participation, pose a significant risk to the participant, or interfere with study data interpretation.
- #14 For Cohorts 1, Stage 1 of Cohort 2, and Cohort 3 only: Congestive heart failure NYHA Class 3 or 4, or participant with a history of congestive heart failure NYHA Class 3 or 4 in the past, unless an echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
- #15 For Cohorts 1, Stage 1 of Cohort 2, and Cohort 3 only: Moderate renal impairment (eGFR < 60 mL/min).
- #16 For Cohorts 1, Stage 1 of Cohort 2 and Cohort 3 only: Moderate hepatic impairment (total bilirubin > 1.5 × ULN). Participants with Gilbert’s Syndrome are allowed with a total bilirubin ≤ 3 × ULN provided that direct (conjugated) bilirubin ≤ ULN, AST and ALT are ≤ 3 × ULN, and there is no evidence of liver disease.
- #17 For Cohort 3 only: FLT3 ITD mutation with VAF of ≥5%
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Andrew Sochacki
Status
Recruiting
Condition(s) Treated at Site
Leukemia