The goal of this clinical trial is to learn if Revumenib in combination with Fludarabine and Cytarabine can treat children with NUP98-rearranged relapsed or refractory Acute Myeloid Leukemia. The main question it aims to answer is:
What is the Best Overall Response Rate by morphologic response criteria after up to two cycles of revumenib in combination with fludarabine and cytarabine (FLA) chemotherapy?
Participants will receive up to two cycles of Revumenib in combination with fludarabine and cytarabine with intrathecal triple therapy. Participant may also receive a stem cell transplant followed by Revumenib monotherapy if it is necessary.
Up to 27 children and young adults will be enrolled.
Recurrent disease with ≥ 5% leukemic blasts by morphology in the bone marrow after having achieved morphologic remission (morph-CR). Patients who have received any other re-induction therapy following relapse will not be eligible.
Morph-CR is defined as attainment of an M1 bone marrow (< 5% morphologic leukemic blasts) no evidence of circulating leukemic blasts or extramedullary disease and with recovery of peripheral blood counts (ANC ≥ 500/µL and platelet count ≥ 50,000/µL).
Cytotoxic Chemotherapy: Must not have received within 14 days of entry onto this study, except for hydroxyurea or cytarabine
Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before enrollment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
Positive blood culture within 48 hours of study enrollment;
Fever above 38.2⁰C within 48 hours of study enrollment with clinical signs of infection. NOTE: Fever that is determined to be due to tumor burden does NOT exclude patients if there are documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
A positive fungal culture within 30 days of study enrollment.
Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections does not exclude patients.
Single group
Revumenib
DrugPatients under 40 kg, and those unable to swallow pills, must receive oral suspension (40 mg/mL): * \< 40 kg: 95 mg/m2 (max 160 mg/dose) orally twice daily * ≥ 40 kg (flat-dose): 160 mg orally twice daily * Round to the nearest markings on the syringe, within 10% of the calculated dose Patients ≥ 40 kg that are able to swallow pills: \- 160 mg orally twice daily
Fludarabine
Drug* 5 mg for patients with BSA 0.25-0.29 * 6.25 mg for patients with BSA 0.3-0.34 * 8.75 mg for patients with BSA 0.35-0.39 * 10 mg for patients with BSA 0.4-0.44 * 12.5 mg for patients with BSA 0.45-0.49 * 15 mg for patients with BSA 0.5-0.54 * 16.25 mg for patients with BSA 0.55-0.59 * 30 mg/m2/dose for patients with BSA \> 0.6
Cytarabine (Ara-C)
Drug* 300 mg for patients with BSA 0.25-0.29 * 420 mg for patients with BSA 0.3-0.34 * 560 mg for patients with BSA 0.35-0.39 * 680 mg for patients with BSA 0.4-0.44 * 820 mg for patients with BSA 0.45-0.49 * 960 mg for patients with BSA 0.5-0.54 * 1100 mg for patients with BSA 0.55-0.59 * 2000 mg/m2/dose for patients with BSA \> 0.6
Methotrexate (IT)
DrugGiven intrathecally * 6 mg for patients \> 30 days - \< 1 year * 8 mg for patients \> 1 - \< 2 years * 10 mg for patients \> 2 - \< 3 years * 12 mg for patients \> 3 years
Hydrocortisone (intrathecal)
DrugGiven intrathecally * 12 mg for patients \> 30 days - \< 1 year * 16 mg for patients \> 1 - \< 2 years * 20 mg for patients \> 2 - \< 3 years * 24 mg for patients \> 3 years
Cytarabine (intrathecal)
DrugGiven intrathecally * 18 mg for patients \> 30 days - \< 1 year * 24 mg for patients \> 1 - \< 2 years * 30 mg for patients \> 2 - \< 3 years * 36 mg for patients \> 3 years
Best Overall Response Rate (BOR) by morphologic response criteria
The best Overall Response rate according to morphologic response (Morph-CR/CRi/CRp) after up to 2 cycles
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