Using revumenib to treat leukemia linked to HOX gene upregulation

A Phase II Study of the Menin Inhibitor Revumenib in Leukemia Associated With Upregulation of HOX Genes

This study is testing if a new drug called revumenib can help people aged 12 and older with certain types of leukemia that are linked to specific gene changes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 2 sites (New York, New York and 1 other locations)
• Trial ID: NCT06229912 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of revumenib, a menin inhibitor, in patients with leukemias characterized by the upregulation of HOX genes. The study aims to determine the drug's effectiveness in controlling these leukemias and includes secondary objectives such as measuring residual disease clearance and assessing overall survival rates. Participants will undergo treatment with revumenib, and various molecular and cellular markers will be evaluated to predict treatment response and resistance. The trial is designed for patients aged 12 and older with specific genetic alterations associated with their leukemia.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 12 and older with relapsed or refractory acute leukemia and specific genetic alterations related to HOX gene upregulation.

Not a fit: Patients without the specified genetic alterations or those with other types of leukemia may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat leukemias linked to HOX gene alterations.

How similar studies have performed: While the approach of targeting HOX gene upregulation is relatively novel, similar studies using menin inhibitors have shown promising results in other hematological malignancies.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 12 years with weight ≥ 40Kg.
2. ECOG performance status of ≤ 2.
3. Relapsed or refractory acute leukemia, of either myeloid, lymphoid or mixed lineages, with genetic alterations associated with upregulation of HOX, as specified below:

   Alteration/Mutation - Cytogenetics KMT2A-PTD = Normal karyotype; NPM1-MLF1 = t(3;5)(q25;q34); NUP98r = 11p15 rearrangements; SET-NUP214 = t(9;9)(q34;q34); RUNX1-EVI1 = t(3;21)(q26;q22); MYST3-CREBBP = t(8;16)(p11;p13); CDX2-ETV6 = t(12;13)(p13;q12); CALM-AF10 = t(10;11)(p13;q14-21); MN1-ETV6 = t(12;22)(p13;q12); UBTF-TD = Normal karyotype
4. WBC must be below 25,000/ uL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
5. Baseline ejection fraction must be \> 40%.
6. Adequate hepatic function (direct bilirubin \< 1.5x upper limit of normal (ULN) unless increase is due leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible).
7. Adequate renal function with an estimated glomerular filtration rate ≥ 60 mL/min based on local institutional practice for age-appropriate determination.
8. Participants or parent/guardian is willing and able to provide informed consent.
9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
10. Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study and at least 3 months after the last treatment.

Exclusion Criteria:

1. Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the participant at unacceptable risk of study treatment.
2. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for participants with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
3. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
4. Participants with concurrent active malignancy under treatment.
5. Known active hepatitis B (HBV) or hepatitis C (HCV) or human immunodeficiency virus (HIV) infections.
6. Female subjects who are pregnant or breast-feeding.
7. Participant has an active uncontrolled infection.
8. Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
9. QTc \>450 msec for males and QTc \>470 msec for females using the Fridericia Formula using an average of the 3 Screening EKGs.
10. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
11. Clinically active central nervous system (CNS) leukemia.
12. Participants on immunosuppressive therapy post-HSCT at the time of screening (must be off all systemic immunosuppression therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks). The use of topical steroids for cutaneous graft-versus-host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone (or equivalent) daily are permitted.
13. Participants with Grade \> 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

Where this trial is running

New York, New York and 1 other locations

• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Ghayas Issa, MD — M.D. Anderson Cancer Center
• Study coordinator: Ghayas Issa, MD

Conditions Leukemia; HOX Gene