Investigating a new oral treatment for acute myeloid leukemia

A Phase I-II Study Investigating the All Oral Combination of the Menin Inhibitor SNDX-5613 With Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE)

This study is testing a new all-oral treatment for people with acute myeloid leukemia to see if it is safe and effective in controlling the disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05360160 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of an all-oral combination therapy involving the menin inhibitor SNDX-5613, decitabine/cedazuridine (ASTX727), and venetoclax for patients with acute myeloid leukemia (AML) or mixed phenotype acute leukemia with a myeloid phenotype (MPAL). The study is divided into two parts: the first part focuses on determining the highest tolerable dose of SNDX-5613, while the second part assesses the effectiveness of this combination in controlling the disease. Participants will be monitored for overall survival, event-free survival, and duration of response, alongside exploratory evaluations of molecular and cellular markers related to treatment response.

Who should consider this trial

Good fit: Ideal candidates include patients aged 12 years and older with newly diagnosed or relapsed/refractory acute myeloid leukemia or mixed phenotype acute leukemia with a myeloid phenotype.

Not a fit: Patients with rapidly proliferative disease or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective oral therapy option for patients with acute myeloid leukemia.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating acute myeloid leukemia, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 12 years with weight ≥ 40Kg.
2. ECOG performance status of ≤ 2.
3. Newly diagnosed (frontline cohort), who are not eligible for high-intensity induction chemotherapy or relapsed/refractory (R/R cohort) AML or myeloid phenotype MPAL with either KMT2Ar, or NUP98r, or NPM1c.
4. WBC must be below 25,000/ μL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
5. Baseline ejection fraction must be \> 40%.
6. Adequate hepatic function (direct bilirubin \< 2x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible).
7. Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease.
8. Willing and able to provide informed consent.
9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
10. Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study and at least 3 months after the last treatment.

Exclusion Criteria:

1. Prior treatment with a menin inhibitor.
2. Patients with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
3. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
4. Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
5. Patients with a concurrent active malignancy under treatment.
6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
7. Female subjects who are pregnant or breast-feeding.
8. Patient has an active uncontrolled infection.
9. 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.
10. QTc \>470 msec using the Fridericia Formula.
11. History of a complete bundle branch block or high-degree atrioventricular block.
12. History of or any concurrent condition, therapy, or laboratory abnormality 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.
13. Clinically active central nervous system (CNS) leukemia.
14. Patients on immunosuppressive therapy post-HSCT at the time of screening with R/R leukemia (must be off all systemic immunosuppression therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks). The use of topical steroids for cutaneous graftversus- host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.
15. Patients with Grade \> 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Ghayas Issa, MD — M.D. Anderson Cancer Center
• Study coordinator: Ghayas Issa, MD

Conditions Acute Myeloid Leukemia