A Study of SNDX-5613 in Combination With Chemotherapy in Participants With Leukemia

Sponsor
Syndax Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05326516
Collaborator
(none)
54
2
2
22.8
27
1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and tolerability of SNDX-5613 when given in combination with 2 different chemotherapy regimens in participants with relapsed/refractory leukemias harboring lysine methyltransferase 2A (KMT2A) or mNPM1.

Condition or Disease Intervention/Treatment Phase
  • Drug: SNDX-5613
  • Drug: Chemotherapy Regimen 1
  • Drug: Chemotherapy Regimen 2
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
54 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The study will use a Bayesian optimal interval (BOIN) design to evaluate the doses and determine the maximum tolerated dose.The study will use a Bayesian optimal interval (BOIN) design to evaluate the doses and determine the maximum tolerated dose.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
AUGMENT-102: A Phase 1, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability and Preliminary Anti-Leukemic Activity of SNDX-5613 in Combination With Chemotherapy in Patients With Relapsed/Refractory Leukemias Harboring a KMT2A/MLL Gene Rearrangement or Nucleophosmin 1 Mutation (mNPM1)
Actual Study Start Date :
Mar 9, 2022
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Feb 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: SNDX-5613 and Chemotherapy Regimen 1

Participants with acute lymphoblastic leukemia/mixed phenotype acute leukemia (ALL/MPAL) will receive SNDX-5613 every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 1.

Drug: SNDX-5613
Participants will receive SNDX-5613 until meeting criteria for discontinuation.

Drug: Chemotherapy Regimen 1
Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide.

Experimental: SNDX-5613 and Chemotherapy Regimen 2

Participants with ALL/MPAL or acute myeloid leukemia (AML) will receive SNDX-5613 every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 2.

Drug: SNDX-5613
Participants will receive SNDX-5613 until meeting criteria for discontinuation.

Drug: Chemotherapy Regimen 2
Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Dose Limiting Toxicities From SNDX-5613 [Day 1 through up to 30 days after last dose of study intervention]

  2. Number of Participants With Treatment-emergent Adverse Events [Day 1 through up to 30 days after last dose of study intervention]

Secondary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) Of SNDX-5613 [Predose through up to 6 hours post dose]

  2. Area Under The Plasma Concentration Versus Time Curve From Time 0 To t (AUC0-t) Of SNDX-5613 [Predose through up to 6 hours post dose]

  3. Area Under The Concentration Versus Time Curve From Time 0 To 24 Hours (AUC0-24) Of SNDX-5613 [Predose through up to 6 hours post dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:
30 Days and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  • Participants must have documented relapsed or refractory (R/R) AML, ALL, or MPAL harboring KMT2A leukemia gene rearrangement or mNPM1.

  • White blood count must be <50,000/microliter at time of enrollment. Participants may receive cytoreduction per protocol prior to beginning SNDX-5613.

  • Eastern Cooperative Oncology Group performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and <18 years); Lansky Performance Score of ≥50 (if aged <16 years).

  • Adequate liver and cardiac function

  • Participant must be taking 1 of the following medications for antifungal prophylaxis: itraconazole, ketoconazole, posaconazole, or voriconazole for at least 7 days prior to the start of study drug.

  • A female of childbearing potential must agree 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.

  • A male of childbearing potential must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.

Key Exclusion Criteria:
  • Isolated extramedullary relapse

  • Any unresolved ≥Grade 2 reversible toxicity from previous anticancer therapy except alopecia or Grade 2 neuropathy

  • Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have discontinued all systemic immunosuppressive therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.

  • 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 (for example, 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. For participants with therapy-related leukemia, primary disease must be in remission for 1-year following completion of therapy.

  • If the participant is known to be human immunodeficiency virus (HIV)-positive, the participant must have undetectable HIV viral load within the previous 6 months.

  • Hepatitis B

  • Hepatitis C

  • 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.

  • QT interval >450 milliseconds

  • Any gastrointestinal (GI) issue of the upper GI tract that might affect oral drug absorption or ingestion (for example, gastric bypass, gastroparesis).

  • Cirrhosis with a Child-Pugh score of B or C

  • Down Syndrome

  • Genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.

  • Participation in another therapeutic interventional clinical study within 28 days of starting.

  • Radiation Therapy: within 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or within 14 days from local palliative radiation therapy (small port).

  • Stem Cell Infusion: within 60 days from hematopoietic stem cell transplantation and within 4 weeks (from first dose) from donor lymphocyte infusion without conditioning.

  • Biologics (for example, monoclonal antibody therapy, antibody-drug conjugates): within 7 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent.

  • Immunotherapy: within 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and within 21 days since receipt of chimeric antigen receptor therapy or other modified T-cell therapy.

  • Hematopoietic Growth Factors: within 7 days since the completion of therapy with short-acting hematopoietic growth factors and within 14 days with long-acting growth factors.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Mercy Hospital Kansas City Missouri United States 64108
2 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229

Sponsors and Collaborators

  • Syndax Pharmaceuticals

Investigators

  • Study Director: Nicole McNeer, M.D., Syndax Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Syndax Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT05326516
Other Study ID Numbers:
  • SNDX-5613-0702
First Posted:
Apr 13, 2022
Last Update Posted:
Jul 21, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Syndax Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 21, 2022