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 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-DE
- Lead Sponsor
- Syndax Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 333
Diagnosis:
1. Patients in Phase 1 Arm A and B must have active acute leukemia harboring Lysine (K) methytransferase 2A (KMT2A) rearrangement or Nucleophosmin (NPM1) mutation as defined by the National Comprehensive Cancer Network (NCCN) Guidelines stated in the protocol.
Patients in Phase 1 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 NCCN guidelines stated in the protocol.
•acute leukemia harboring an KMT2A rearrangement, Nucleporin 98 (NUP98) rearrangement, or NPM1 mutation that have detectable disease in the bone marrow not meeting criterion for active leukemia as described above.
2. Phase 1:
• 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 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.
•Arms E: Patients must not be receiving any weak, moderate, or strong
CYP3A4 inhibitors/inducers for at least 7 days prior to enrollment and
while on SNDX5613 treatment.
• Arm F: Patients must be receiving isavuconazole for at least 7 days prior to enrollment and while on SNDX-5613
treatment. Patients must not be receiving any other weak, moderate, or
strong CYP3A4 inhibitors/inducers.
3. Phase 2: Documented R/R acute leukemia:
Cohort 2A: Documented R/R ALL/MPAL with a KMT2A rearrangement.
Cohort 2B: Documented R/R AML with a KMT2A rearrangement.
Cohort 2C: Documented R/R AML with NPM1m.
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. Patients who have <5% blasts in the bone marrow at baseline may be replaced to ensure a sufficient number of patients for the efficacy analyses.
Age/Weight:
5. Male or female patients aged >=6 months. Patients intend to receive SNDX-5613 in combination with cobicistat must weigh =35 kg. See Protocol Section 10.11.3.1 for age of inclusion criteria in Germany.
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
Diagnosis:
1. Diagnosis of active acute promyelocytic leukemia.
2. Isolated extramedullary relapse (Phase 2 only).
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, or positive HBV
deoxyribonucleic acid [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.Please refer to the protocol for the list of exclusion that apply to related to concomitant use of CYP3A4 inhibitors or inducers (Phase 1 and Phase 2).
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 prolongation that are used as standard supportive therapies and the azoles permitted in the relevant arms of Phase 1 and in Phase 2. Please see Appendix 10.7 of the protocol for examples of medications that may be appropriate substitutes for such medications.
Please refer to
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