A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation

  • STATUS
    Recruiting
  • End date
    Jan 1, 2024
  • participants needed
    186
  • sponsor
    Syndax Pharmaceuticals
Updated on 12 May 2021
Investigator
Sue Fischer
Primary Contact
Florida Cancer Specialists and Research Institute (5.4 mi away) Contact
+8 other location
cancer
myeloid leukemia
total body irradiation
acute leukemia
prednisone
blast cells
hematopoietic growth factors

Summary

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of SNDX-5613 in patients with acute leukemia.

In Phase 2, patients will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613.

Description

Phase 1 dose escalation will determine the maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of SNDX-5613 in patients with acute leukemia harboring an MLL rearrangement or NPM1 mutation:

  • Arm A: Patients not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/ inducers.
  • Arm B: Patients receiving strong cytochrome P450 3A4 (CY3A4) inhibitors for antifungal prophylaxis.
  • Arm C: Patients receiving SNDX-5613 in combination with cobicistat.

In Phase 2, patients will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613:

  • Cohort 2A: Patients with MLLr acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL).
  • Cohort 2B: Patients with MLLr AML.
  • Cohort 2C: Patients with NPM1c AML.

Details
Condition childhood ALL, Acute myeloid leukemia, Acute Myelogenous Leukemia (AML), Mixed Phenotype Acute Leukemia, Acute Leukemia of Ambiguous Lineage, Lymphocytic Leukemia, Acute, Mixed Lineage Acute Leukemia, acute lymphoblastic leukemia, leukemia, acute lymphoblastic, acute lymphoid leukaemia, acute lymphocytic leukemia, acute lymphoblastic leukemia (all), acute myelogenous leukemia, anll, acute myeloblastic leukemia
Treatment Cobicistat, SNDX-5613
Clinical Study IdentifierNCT04065399
SponsorSyndax Pharmaceuticals
Last Modified on12 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients 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
2020) and Acute Myeloid Leukemia (Version 3.2020)
Phase 1: Documented R/R acute leukemia harboring MLL rearrangement or NPM1c mutation
Arm A: Patients not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers
Arm B: Patients receiving strong cytochrome P450 3A4 inhibitors for antifungal prophylaxis
Phase 2
Arm C: Patients receiving SNDX-5613 in combination with cobicistat
Cohort 2A: Documented R/R ALL/MPAL with an MLLr translocation
Cohort 2B: Documented R/R AML with an MLLr translocation
Cohort 2C: Documented R/R AML with NPM1c
WBC must be below 50,000/ L at time of enrollment. Patients may receive cytoreduction prior to enrollment
Male or female patient aged 30 days old
Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score 40
Any prior treatment-related toxicities resolved to Grade 1 prior to enrollment, with the exception of Grade 2 neuropathy or alopecia
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)
Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion (DLI) without conditioning
Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy
Myelosuppressive Chemotherapy: At least 14 days since the completion of cytotoxic/myelosuppressive 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 7 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent
Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to 10 mg prednisone daily) or cytoreductive therapy
Adequate organ function
If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose

Exclusion Criteria

Patients meeting any of the following criteria are not eligible for study
participation
Active diagnosis of acute promyelocytic leukemia
Isolated extramedullary relapse
Known CNS involvement (cytologic or radiographic)
Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Patients with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment
Hepatitis B or C
Pregnant or nursing women
Cardiac Disease
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
QTc >450 msec for males and QTc >450 msec for females. 8. Gastrointestinal Disease
Cirrhosis with a Child-Pugh score of B or C. 9. Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant patients must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Patients may be on physiological doses of steroids. 10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe. 11. Participation in another therapeutic interventional clinical study within 30 days of enrollment
Chronic diarrhea or other gastrointestinal issue that might affect oral drug absorption or ingestion (ie, short-gut syndrome, gastroparesis, etc)
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