A Phase II Study of the Menin Inhibitor Revumenib in Leukemia Associated With Upregulation of HOX Genes
To learn if revumenib (also known as SNDX-5613) can help to control leukemias associated with an increase in expression of HOX genes.
• Age ≥ 12 years with weight ≥ 40Kg.
• ECOG performance status of ≤ 2.
• 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
• WBC must be below 25,000/ uL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
• Baseline ejection fraction must be \> 40%.
• 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).
• Adequate renal function with an estimated glomerular filtration rate ≥ 60 mL/min based on local institutional practice for age-appropriate determination.
• Participants or parent/guardian is willing and able to provide informed consent.
• 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.
⁃ 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.