Brief Title
A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation
Official Title
AUGMENT-101: A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX 5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation
Brief 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.
Detailed 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.
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Occurrence of dose-limiting toxicities (DLTs) (Phase 1)
Secondary Outcome
Composite definition of complete remission (CRc) Rate (Phase 2)
Condition
Acute Myeloid Leukemia
Intervention
SNDX-5613
Study Arms / Comparison Groups
Experimental: SNDX-5613
Description: Phase 1: Oral SNDX-5613; sequential cohorts of escalating dose levels of SNDX-5613 to identify the maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D). Patients will be enrolled in one of two dose-escalation arms: 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: Oral SNDX-5613; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
186
Start Date
November 5, 2019
Completion Date
January 1, 2024
Primary Completion Date
July 1, 2022
Eligibility Criteria
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 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
1. 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.
2. Phase 2:
- 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.
3. WBC must be below 50,000/ μL at time of enrollment. Patients may receive cytoreduction
prior to enrollment.
4. Male or female patient aged ≥30 days old.
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or
Karnofsky/Lansky score ≥40.
6. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with
the exception of ≤Grade 2 neuropathy or alopecia.
7. 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).
8. 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.
9. 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.
10. Myelosuppressive Chemotherapy: At least 14 days since the completion of
cytotoxic/myelosuppressive therapy.
11. 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.
12. Biologics: At least 7 days or 5 half-lives, whichever is longer, since the completion
of therapy with a biologic agent.
13. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving
physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy.
14. Adequate organ function.
15. 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:
1. Active diagnosis of acute promyelocytic leukemia.
2. Isolated extramedullary relapse.
3. Known CNS involvement (cytologic or radiographic).
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 or C.
6. Pregnant or nursing women.
7. 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 >470 msec for females.
8. Gastrointestinal Disease:
- Chronic diarrhea or other gastrointestinal issue that might affect oral drug
absorption or ingestion (ie, short-gut syndrome, gastroparesis, etc).
- 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.
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Galit Rosen, M.D., 781-419-1400, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04065399
Organization ID
SNDX-5613-0700
Responsible Party
Sponsor
Study Sponsor
Syndax Pharmaceuticals
Study Sponsor
Galit Rosen, M.D., Study Director, Syndax Pharmaceuticals, Inc.
Verification Date
November 2020