ALLG BM15: A Double-blind, Phase I/II, Randomised Study to Compare the Efficacy of Enzomenib Versus Placebo as Maintenance after Allogeneic Haematopoietic Stem Cell Transplantation in Subjects with Acute Myeloid Leukaemia (AML).
A Double-blind, Phase I/II, Randomised Study to Compare the Efficacy of Enzomenib Versus Placebo as Maintenance after Allogeneic Haematopoietic Stem Cell Transplantation in Subjects with Acute Myeloid Leukaemia (AML).
Australasian Leukaemia and Lymphoma Group
53 participants
Jul 1, 2026
Interventional
Conditions
Summary
What the study is about: This study will evaluate whether Enzomenib, a menin inhibitor, can reduce relapse risk when given as maintenance therapy after allogeneic haematopoietic stem cell transplantation in patients with acute myeloid leukaemia (AML). Who is it for: It is for patients aged 12 years or older with AML subtypes known to be sensitive to menin inhibition, including those with NPM1 mutations or KMT2A rearrangements, who will undergo an allogeneic haematopoietic stem cell transplantation. Study details: This is a double-blind, randomised Phase II trial comparing oral Enzomenib (up to 200 mg) with placebo for up to 24 months post-transplant. The first 20 participants will enter a safety run-in after atleast 2 cycles of Enzomenib treatment, before expanding to 170 patients across UK, Australian, and New Zealand centres. A target population of 53 will be recruited from the Australian and New Zealand centres. What is hoped from it: The study aims to determine whether Enzomenib can improve relapse-free survival compared to placebo, reduce the risk of disease recurrence, and provide a well-tolerated maintenance option after allogeneic haematopoietic stem cell transplantation for high-risk AML patients.
Eligibility
Inclusion Criteria25
- Randomisation will take place following allogeneic HCT after all randomisation eligibility are met. Screening for randomisation will be assessed between day 28 to day 100. Participants must be able to commence study therapy between day 42 and 100 post-HCT.
- Patients must satisfy the following criteria to be enrolled in the study:
- Age greater than or equal to twelve years at the time of signing the informed consent form.
- Able to swallow oral medication and commence study therapy by Day ninety-eight after Haematopoietic Cell Transplantation (HCT).
- In remission, according to the following criteria:
- a. At the time of Haematopoietic Cell Transplantation:
- i. Bone marrow blast count less than or equal to five percent, confirmed by morphology and/or immunophenotyping.
- b. Post-transplant bone marrow:
- i. Bone marrow blast count less than or equal to five percent, confirmed by morphology and/or immunophenotyping.
- Sustained neutrophil and platelet engraftment, defined as:
- a. Absolute Neutrophil Count (ANC) greater than or equal to one point zero times ten to the power of nine per litre on two consecutive tests at least seven days apart, unsupported by myeloid growth factors. One test must be within seven days of randomisation.
- b. Platelet count greater than or equal to fifty times ten to the power of nine per litre on two consecutive tests at least seven days apart without platelet transfusion during the screening period. One test must be within seven days of randomisation.
- Serum Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) less than three times the upper limit of normal (ULN).
- Serum bilirubin less than two times the upper limit of normal (ULN). Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (that is, ineffective erythropoiesis) or Gilbert’s syndrome.
- Serum creatinine less than two times the upper limit of normal (ULN).
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to two.
- Patients with a history of acute Graft-versus-Host Disease (GvHD) are eligible if they meet the following criteria:
- a. Acute Graft-versus-Host Disease less than Grade Two at the time of randomisation.
- b. Systemic corticosteroids are administered at a dose equivalent to prednisone less than or equal to zero point five milligrams per kilogram, if the dose is stable for at least two weeks prior to randomisation.
- c. Topical steroids are permitted.
- Females of childbearing potential may participate, providing they meet the following conditions:
- a. Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomised partner) or practice true abstinence throughout the study and for six months following the last dose of study therapy; and
- b. Have a negative serum or urine pregnancy test (sensitivity of at least twenty-five milli-international units per millilitre) at screening; and
- c. Have a negative serum or urine (investigator’s discretion) pregnancy test (sensitivity of at least twenty-five milli-international units per millilitre) within seventy-two hours prior to starting study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
- Male patients with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for three months following the last dose of study therapy.
Exclusion Criteria24
- Randomisation will take place following allogeneic HCT after all randomisation eligibility are met. Screening for randomisation will be assessed between day 28 to day 100. Participants must be able to commence study therapy between day 42 and 100 post-HCT.
- Use of any of the following after transplantation and prior to starting study therapy:
- a. Any chemotherapy used for adjuvant therapy.
- b. Unlicensed investigational agents or therapies used within twenty-eight days prior to starting study therapy.
- c. Azacitidine, decitabine, or other hypomethylating agents.
- Measurable Residual Disease (MRD) relapse at the time of randomisation based on European Leukaemia Net (ELN) criteria
- Result must be rapidly confirmed on a second consecutive sample obtained from the same tissue source, preferably bone marrow, to confirm MRD relapse.
- Active Graft-versus-Host Disease (GvHD) Grade Two or higher (acute GvHD Clinical Staging and Grading, Glucksberg criteria).
- Concurrent use of corticosteroids equivalent to prednisone at a dose greater than zero point five milligrams per kilogram.
- Active uncontrolled viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV).
- Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs or symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
- History of prior malignancies, except:
- Lobular breast carcinoma in situ.
- Fully resected basal cell or squamous cell carcinoma of the skin.
- Treated cervical carcinoma in situ.
- Incidental histologic finding of prostate cancer (T1a or T1b using the Tumor, Node, Metastasis (TNM) clinical staging system).
- Previous Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukaemia (CMML), or Myeloproliferative Neoplasm (MPN) resulting in secondary Acute Myeloid Leukaemia (AML).
- Cancer treated with curative intent greater than or equal to three years previously will be allowed.
- Cancer treated with curative intent less than three years previously will not be allowed.
- Pregnant or lactating females.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if they were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Corrected QT interval using Fridericia’s formula (QTcF): females greater than or equal to four hundred seventy milliseconds and males greater than or equal to four hundred fifty milliseconds.
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Interventions
Patients will be randomised to Enzomenib as maintenance therapy (Arm 1-Intervention) vs placebo (Arm 2-Control) after allogeneic haematopoietic stem cell transplantation. Treatment cycles are 28 days long. Enzomenib will initially be administered orally at a dose of 100mg for 2 cycles. From cycle 3 onwards, Enzomenib will be administered orally twice daily for a total dose of 200mg, for up to 2 years post-HCT. Patients will commence therapy between days 42 and 100 post-transplant up to a maximum of 24 months post-transplant. Treatment will be continuous throughout the 24 month period. The first 20 randomised patients will be enrolled in a phase 1 safety run-in and will receive at least 2 cycles of Enzomenib. The Data Monitoring Committee (DMC) will review outcomes to confirm the safety of Enzomenib maintenance post-transplant, before moving into the randomised Phase II study. A total of 170 patients (inclusive of the Phase 1 safety run-in patients) will be enrolled with 53 patients recruited across Australia and New Zealand. The treatment start date will be determined after the patient completes all screening assessments and eligibility is confirmed. The overall duration will follow the protocol-defined schedule (e.g., number of cycles or until disease progression, unacceptable toxicity, withdrawal of consent). The study team and data monitoring committee will review patient response and tolerability at scheduled visits to determine continuation or discontinuation of therapy. Monitoring of adverse events and tolerability is continuous. All treatment will be administered by the study team (i.e., registered nurse, the lead physician, physicians listed on the trial to assist the lead physician). Drug accountability will be performed by the administering institutions to assess compliance.
Locations(2)
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ACTRN12626000019303