A study to investigation 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 LeukemiasMedDRA version: 20.1Level: LLTClassification code 10024330Term: Leukemia acuteSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004104-34-NL
- 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
- 222
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 NCCN in the NCCN Clinical Practice Guidelines in Oncology for Acute Lymphoblastic Leukemia (Ver 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
Patients in Arm C, Arm D, Arm E and Arm F 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, NUP98 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 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. Refractory or relapsed leukemia is defined by presence of =5% blasts in the bone marrow and/or persistence or reappearance of peripheral blasts.
• All patients must have white blood cell (WBC) count 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 Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant (HSCT) and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion (DLI) .
10. Immunotherapy: At least 42days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21days since receipt of chimeric antigen receptor therapy or other modified T cell therapy.
11. Antileukemia Therapy: At least 14days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy with the exceptions as defined in the protocol.
12. Hematopoietic Growth Factors: At least 7days since the completion of therapy with short-acting hematopoietic growth factors and 14days with long-acting growth factors.
See protocol for additional inclusion criteria.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 133
F.1.3 Elderly (>=65 y
Diagnosis:
1. Active diagnosis of acute promyelocytic leukemia.
2. Isolated extramedullary relapse.
3. Active CNS disease. Refer to the protocol for further details.
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 reflex to 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, life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
• QTc using Fridericia’s correction >450 msec.
9. Gastrointestinal (GI) Disease:
• Any GI 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.
11. 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 treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the patient is not receiving any systemic therapy or radiation.
12. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe.
13. History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the Investigator's opinion
might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate.
Concomitant Medications and Interventions:
14. Any commercially available or investigational antileukemic therapy other than SNDX-5613, with exceptions as defined in the protocol.
15. In Phase 2: Concurrent use of moderate or strong CYP3A4 inhibitors/inducers (except for systemic itraconazole, ketoconazole,
posaconazole, or voriconazole). The acceptable azoles should have been started at least 7 days prior to enrollment. Other moderate or strong
inhibitors or inducers of CYP3A4 should be discontinued at least 7 days prior to enrollment.
16. Phase 1 and Phase 2: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with
the exception of drugs with low risk of QT/QTc prol
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