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 REVUMENIB

What's the purpose of this trial?

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia. In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

Participants 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), or acute leukemia harboring KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.

1. Phase 1:

* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
* Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
* Arm C: Participants receiving revumenib in combination with cobicistat.
* Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
* Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
2. Phase 2:

Documented R/R active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the NCCN Guidelines® for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
* Cohort 2A: Documented R/R ALL/MPAL with KMT2A rearrangement.
* Cohort 2B: Documented R/R AML with KMT2A rearrangement.
* Cohort 2C: Documented R/R AML with NPM1m.
3. White blood cell count below 25,000/ microliter at time of enrollment. Participants may receive cytoreduction prior to enrollment per protocol-specified criteria.
4. Male or female participants aged ≥30 days old.
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥50.
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 hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
9. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T or NK cell therapy.
10. Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic 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 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
13. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing 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:

Participants meeting any of the following criteria are not eligible for study participation:

1. Diagnosis of active acute promyelocytic leukemia.
2. Isolated extramedullary relapse (Phase 2 only).
3. Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
4. Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants 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.
* Corrected QT interval (QTc) \>450 milliseconds.
8. Gastrointestinal Disease:

* any gastrointestinal issue of the upper GI tract that might affect oral drug absorption or ingestion (that is, gastric bypass, 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 participants must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants 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 (for example, breast carcinoma, cervical cancer in situ, melanoma 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 participant is not receiving any systemic therapy or radiation.
11. In Phase 1 and Phase 2: Participants 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 (for example, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1 and in Phase 2.

Additional Trial Information

Phase 1/2

Enrollment: 413 patients (estimated)

View More

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Stanford University Cancer Institute (Palo Alto)

Stanford, CA

Open and Accepting

Colorado

University of Colorado Cancer Center Anschutz Cancer Pavilion

Aurora, CO

Open and Accepting

Florida

Florida Cancer Specialists Sarasota Cattlemen

Sarasota, FL

Open and Accepting

Georgia

Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting

Illinois

University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Open and Accepting

Iowa

Massachusetts

Dana-Farber Cancer Institute

Boston, MA

Open and Accepting

Missouri

Alvin J. Siteman Cancer Center Washington University Medical Campus

St. Louis, MO

Open and Accepting

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting

Memorial Sloan Kettering Commack

Commack, NY

Open and Accepting

Montefiore Medical Center (Moses Campus)

The Bronx, NY

Open and Accepting

North Carolina

Duke Cancer Center Duke University Medical Center

Durham, NC

Open and Accepting

Ohio

Oregon

Oregon Health and Science University OHSU Knight Cancer Institute

Portland, OR

Open and Accepting

Pennsylvania

Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
Interested in this trial?
  • Call us today 😀 keyboard_arrow_right

    We know how difficult and confusing this process can be. If you are interested in this clinical trial or have questions, you can call us at any time. You can also send us a direct message with questions.

    (888) 828-2206
  • If you are interested in keeping an eye on this trial, you can add it to your list of favorite trials. We'll send you alerts when this trial is updated.

  • Talk to your doctor keyboard_arrow_right

    You can print an overview of this trial to take in to your next appointment. Your doctor can help you understand if this trial may be right for you.

Still need help? Send us a message