Testing revumenib with cobicistat for acute myeloid leukemia

Inclusion

• +Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥50.
• +Participants must have active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.
• +ArmArmOne of the groups in a study, each receiving something different.Read more → A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
• +Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
• +Arm C: Participants receiving revumenib in combination with cobicistat.
• +Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
• +Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
• +Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
• +Documented R/R active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the NCCN Guidelines® for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
• +CohortCohortA group of participants sharing a characteristic, followed together.Read more → 2A: Documented R/R ALL/MPAL with KMT2A rearrangement.
• +Cohort 2B: Documented R/R AML with KMT2A rearrangement.
• +Cohort 2C: Documented R/R AML with NPM1m.
• +Cohort 2D: Documented R/R acute leukemia with a genetic mutation expected to lead to HOX/MEIS upregulation (for example, KMT2Ar, NPM1m, and NUP98r), including participants who are MRD-positive by multiparametric flow cytometry or molecular methods only, and including participants with isolated extramedullary disease.
• +White blood cell count below 25,000/ microliter at time of enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →. Participants may receive cytoreduction prior to enrollment per protocolProtocolThe detailed plan a study must follow.Read more →-specified criteria.
• +Male or female participants aged ≥30 days old. Participants intended to receive SNDX-5613 in combination with cobicistat must weigh ≥35 kilograms (kg). Participants in Cohort 2D must be ≥18 years of age and have a body weight ≥40 kg.
• +Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia.
• +Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → and Phase 2Phase 2A middle-stage study looking at what a treatment does and watching for side effects.Read more → Cohorts 2A-2C only:
• +Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
• +Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy.
• +Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
• +Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
• +Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing or cytoreductive therapy.
• +Phase 2 Cohort 2D only:
• +At least 14 days since any other investigational or commercially available antileukemic therapy, with the following exceptions:
• +Cytoreductive therapy with hydroxyurea, low-dose cytarabine (20 mg/square meter (m\^2)/day subcutaneously \[SC\] for 10 days) or low-dose etoposide (up to 200 mg/day orally for 10 days) may be administered concurrently with SNDX-5613.
• +Steroids at physiologic dosing (equivalent to ≤10 mg prednisone daily for participants ≥18 years or ≤10 mg/m\^2/day for participants \<18 years) or for cytoreductive therapy.
• +Adequate organ function.
• +If of childbearing potential, willing to use a highly effective method of contraception from the time of enrollment through 120 days following the last study drug dose.
• +Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
• +Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T or NK cell therapy.
• +Intrathecal chemotherapy for CNS prophylaxis is permitted at the treating physician's discretion.