A study to investigate the short- and long-term safety and tolerability of the drug SNDX-5613 in Patients with Relapsed/Refractory Leukemias. Various doses of SNDX-5613 will be investigated.
- Conditions
- Relapsed or Refractory Acute LeukemiasTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004104-34-IT
- Lead Sponsor
- SYNDAX PHARMACEUTICALS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 333
Diagnosis:
1. Patients in Arms A and B must have active acute leukemia harboring mixed lineage leukemia (MLL) rearrangement or NPM1c mutation as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Acute Lymphoblastic Leukemia (Ver 1.2020) and Acute Myeloid Leukemia (Ver 3.2020).
Patients in Arm C and Arm D must meet one of the following 2 criteria:
•active acute leukemia (bone marrow blasts =5% or reappearance of blasts in
peripheral blood) as defined by the guidelines above.
•acute leukemia harboring an MLL rearrangement or Nucleophosmin 1 mutation (NPM1c) mutation that have detectable disease in the bone marrow not meeting criterion for active leukemia as described above.
2. Phase 1: Documented R/R acute leukemia:
• Arm A: Patients must not be receiving any strong CYP3A4 inhibitor/inducers or fluconazole. Patients who were receiving a strong CYP3A4 inhibitor/inducer or fluconazole must have discontinued the medication at least 7days prior to enrollment.
• Arm B: Patients must be receiving itraconazole, ketoconazole, posaconazole, or voriconazole for antifungal prophylaxis for at least 7days prior to enrollment and while on SNDX-5613 treatment. Patients must not be receiving any other strong CYP3A4 inhibitors/inducers.
• Arm C: Patients must weigh =35 kg and be willing to receive daily cobicistat from C1D2 for at least 28 days. Patients must not be receiving any other strong or moderate CYP3A4 inhibitors/inducers. Patients who were receiving a moderate/strong CYP3A4 inhibitor/inducer must have discontinued the medication at least 7days prior to enrollment.
Arm D: Patients must be receiving fluconazole (moderate CYP3A4 inhibitor) for at least 7 days prior to enrollment and while on SNDX-5613 treatment. Patients must not be receiving any other strong or moderate CYP3A4 inhibitors/inducers.
3. Phase 2: Documented R/R acute leukemia:
Cohort 2A: Documented R/R acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL) with a mixed lineage leukemia-rearranged (MLLr) translocation.
Cohort 2B: Documented R/R AML with an MLLr translocation.
Cohort 2C: Documented R/R AML with NPM1c.
Mutational status is to be reviewed locally to determine patient eligibility in Phase 2 and confirmed centrally.
Disease Status:
4. Recurrent or refractory AML/ALL or MPAL, as defined by standardized criteria after standard of care therapy. Patients with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment are eligible.
• White blood cell (WBC) count must be below 25,000/µL at time of enrollment.
Patients may receive cytoreduction prior to enrollment.
Age/Weight:
5. Male or female patient aged =30 days. Patients intend to receive SNDX-5613 in combination with cobicistat must weigh =35 kg.
Performance Level:
6. Eastern Cooperative Oncology Group performance status score 0-2 (if aged =18yrs); Karnofsky Performance Scale of =50 (if aged =16yrs and <18yrs); Lansky Performance Score of =50 (if aged <16yrs).
Prior Therapy:
7. Any prior treatment-related toxicities resolved to =Grade 1 prior to enrollment, with the exception of =Grade 2 neuropathy or alopecia.
8. 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).
9. Stem
Diagnosis:
1. Active diagnosis of acute promyelocytic leukemia.
2. Isolated extramedullary relapse.
3. Active CNS disease (cytologic or radiographic). Refer to the protocol for details of patients that are required to have a lumbar puncture or Ommaya reservoir tap during the screening period.
Infection:
4. 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.
5. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core antibody alone with positive HBV DNA.
6. Hepatitis C (defined as positive hepatitis C [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]).
Pregnancy and Breast-Feeding:
7. Pregnant or nursing women. Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Concurrent Conditions:
8. 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 using Fridericia’s correction (QTcF) >450 msec.
9. Gastrointestinal Disease:
• Any gastrointestinal issue of the upper GI tract likely to affect oral drug absorption or ingestion.
• Cirrhosis with a Child-Pugh score of B or C.
10. 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.
For the other exclusion criteria pls refer to study protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method