A Phase I/II, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia
Study Identifier:
75276617ALE1001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
Considering participating in a START clinical trial?
Study Summary
To determine the recommended Phase 2 dose(s) (RP2D[s]) of bleximenib in phase 1 (Part 1 [Dose Escalation] and to determine the safety and tolerability at RP2D in Phase 1 Part 2 (Dose expansion).
The purpose of the Phase 2 part of the study is to evaluate the efficacy of bleximenib at the RP2D.
To determine the RP2D of bleximenib and establish the safety and tolerability at the RP2D.
To explores the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of bleximenib at the RP2D.
Adverse events (AEs) are graded using the CTCAE v5.0. The safety dataset comprises pts who have received at least one dose of bleximenib. Efficacy responses are investigator-assessed per modified ELN 2017 in pts with R/R NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) AL.
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.
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.
I/II
Sex
Female & Male
Age
2+ years
Study Drug
Read More
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Age 2 years and above (pediatric cohort only), all other cohorts 18 years and above Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A), nucleophosmin 1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214) alterations Phase: 2 Participants greater than 18 years are eligible Must have had an initial diagnosis of acute myeloid leukemia (AML) per the WHO 2022 classification criteria and have relapsed/refractory disease AML harboring KMT2A-r (gene rearrangement/translocation) or NPM1 mutations only For Both Phase 1 and 2: Pretreatment clinical laboratory values meeting the following criteria: (a) Hematology: white blood cell (WBC) count less than or equal to (<=) 20*10^9/liter (L) and (b) renal function; For adult participants, estimated or measured glomerular filtration rate greater than equal (>=) 30 milliliter per minute (mL/min) per four variable MDRD equation. For pediatric participants an estimated or measured glomerular filtration rate >50 mL/min per the CKiD (Chronic Kidney Disease in Children) Schwartz formula Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Pediatric participants only: Performance status >=70 by Lansky scale (for participants less than [<]16 years of age) or >=70 Karnofsky scale (for participants >=16 years of age) A female of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
- Willing and able to comply with the prohibitions and restrictions stipulated in this plan.
Exclusion criteria
- Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to World Health Organization (WHO) 2016 criteria Active central nervous system (CNS) disease Prior solid organ transplantation QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or for females >= 470 msec. Participants with a family history of Long QT syndrome are excluded Exclusion criteria related to stem cell transplant: a. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; b. Has evidence of graft versus host disease; c. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; d. Requires immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement) Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)
- 1Patients with acute promyelocytic leukemia, diagnosed with Down syndrome-related leukemia, or juvenile myelomonocytic leukemia2Active central nervous system leukemia.3Previous solid organ transplantation.4Cardiovascular disease that may increase the risk of torsades de pointes, or cardiovascular disease diagnosed within 6 months prior to the first administration of the investigational drug.5Any toxicity resulting from previous anticancer treatment that has not subsided to baseline or is ≤ grade 1 (excluding hair loss, stable peripheral neuropathy, thrombocytopenia, neutropenia, and anemia).6Lung damage requiring oxygen therapy to maintain adequate blood oxygen saturation.7Report a body temperature >100.5℉/38℃ within 48 hours prior to the first administration of the study drug.8Known allergies, hypersensitivity reactions, or intolerances to Bleximenib or its excipients.9Exclusion criteria related to stem cell transplantation: a. Received allogeneic bone marrow or hematopoietic stem cell transplantation within ≤3 months prior to the first administration of the investigational drug. b. Evidence of graft-versus-host disease. c. Received donor lymphocyte infusion within ≤1 month prior to the first administration of the investigational drug. d. Required immunosuppressant therapy.10Phase I and II (Cohorts A1 and A2): Patients who have previously received any Menin-KMT2A inhibitors11Patients who have received prior anticancer immunotherapy within 4 weeks prior to enrollment, or who have received belintolimab within 2 weeks prior to enrollment.12Receive the live attenuated vaccine within 4 weeks prior to the first dose of the investigational drug or during the planned administration of the investigational drug; or receive the experimental vaccine within 2 weeks prior to the first dose of the investigational drug.13Those who have received experimental interventions or used invasive experimental medical devices within 2 weeks prior to the planned first dose of the investigational drug, or who are currently enrolled in another clinical study.14Subjects who have undergone major surgery within two weeks prior to the first administration of the investigational drug or who have not yet recovered from surgery must not have major surgery scheduled during the administration of the investigational drug.15It is necessary to use prohibited drugs that cannot be discontinued, substituted, or temporarily interrupted during the study.16Known to be HIV positive or tested positive at screening, unless the viral load is undetectable and the CD4 count is higher than 200 after receiving stable high-efficiency antiretroviral therapy.17The protocol defines active/chronic hepatitis B or hepatitis C infection or clinically active infectious liver disease.18The presence of any serious underlying medical or mental illness, such as epilepsy or mental disorders (such as alcohol or drug abuse), dementia, or altered mental status.19There is evidence that subjects had any active or uncontrolled infection within 7 days prior to the first dose of the investigational drug.20Those who cannot take oral medication, or who have a disease that may affect the absorption of the study drug, or who have undergone previous surgical resection.twenty oneThere are any circumstances where the researcher believes that participation in this study does not provide the maximum benefit to the participants or may hinder, limit, or confound the assessments required by the study protocol.twenty twoThis study investigated active malignant tumors other than those treated with this disease.twenty threePatients diagnosed with Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.
Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Gala Vega Achabal
Status
Recruiting
Condition(s) Treated at Site
Leukemia
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Andrew Sochacki
Status
Recruiting
Condition(s) Treated at Site
Leukemia