AML (Acute Myeloid Leukemia)
Conditions
Keywords
CHM-029, AML, Menin, leukemia, NPM1, KMT2A, NUP98, Charm
Brief summary
The goal of this study is 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. The main questions the study aims to answer are: * What is an appropriate dose of CHM-029? * What side effects may occur with CHM-029? * How does the body process CHM-029? Researchers will evaluate increasing dose levels of CHM-029 to better understand its safety and how the body responds to treatment. Participants will visit the study clinic regularly for safety assessments, blood tests, electrocardiograms (ECGs), and bone marrow evaluations to monitor their health and response to treatment.
Detailed description
CHM-029-01 is a Phase 1/2, first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antileukemic activity of orally administered CHM-029 in adults with relapsed or refractory acute myeloid leukemia (AML) with an NPM1 mutation, KMT2A rearrangement, or NUP98 rearrangement.
Interventions
DRUGCHM-029
CHM-029 is administered orally.
Sponsors
Charm Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) | Baseline through Day 28 | A DLT is defined as any Adverse Event (AE) which meets DLT criteria, not clearly due to the underlying disease or extraneous causes, that occurs within the DLT observation period. |
| Number of participants with adverse events (AEs) | Baseline through study completion, an average of 3 years | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of participants with adverse events (AEs) by severity | Baseline through study completion, an average of 3 years | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0 |
| Number of participants with laboratory value abnormalities and/or adverse events (AEs) | Baseline through study completion, an average of 3 years | Number of participants with potentially clinically significant laboratory values. |
| Rates of dose modification due to adverse events (AEs) according to NCI CTCAE | Baseline through study completion, an average of 3 years | Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.6.0 |
| Maximum tolerated dose (MTD) and/or optimal biological dose (OBD) of CHM-029 | Baseline through study completion, an average of 3 years | Maximum tolerated dose or optimal biological dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) profile of CHM-029: Plasma concentrations | Baseline through study completion, an average of 3 years | Maximum plasma concentrations of CHM-029 will be reported. |
| Pharmacokinetic (PK) profile of CHM-029: Area under the curve | Baseline through study completion, an average of 3 years | Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC) |
| Pharmacokinetic (PK) profile of CHM-029: Time of maximum concentration (Tmax) and half-life (T1/2) | Baseline through study completion, an average of 3 years | Pharmacokinetic parameters will be calculated using standard non-compartmental techniques |
| Complete remission and complete remission with partial hematological recovery (CR/CRh) rate | Baseline to study completion, an average of 3 years | The CR/CRh rate is defined as the number of participants who achieved either CR or CRh at any of the post baseline visits divided by the number of participants in the analysis population. |
| Composite complete remission rate (CRc) | Baseline through study completion, an average of 3 years | The number of participants who achieve an overall response of complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), or complete remission with incomplete platelet recovery (CRp) at any post-baseline assessment, according to protocol-defined response criteria, divided by the number of participants in the analysis population. |
| Duration of response (DOR) | Baseline through study completion, an average of 3 years | DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. |
| Morphological leukemia free state (MLFS) rate | Baseline through study completion, an average of 3 years | The MLFS rate is defined as the number of participants who achieved MLFS at any post-baseline assessment, according to protocol-defined response criteria, divided by the number of participants in the analysis population. |
| Best response rate | Baseline through study completion, an average of 3 years | The number of participants who achieved a best overall response of CRc or MLFS, according to protocol-defined response criteria, divided by the number of participants in the analysis population. |
| Overall survival (OS) | Baseline through study completion, an average of 3 years | OS is defined from the date of first dose of study treatment to the date of death due to any cause. |
| Event free survival (EFS) | Baseline through study completion, an average of 3 years | EFS is defined as the number of days from the date of enrollment to the date of earliest evidence of relapse, treatment failure, or death. |
Countries
United States
Contacts
CONTACTCharm Study Contact
Outcome results
None listed