Testing BXCL701 for treating relapsed or refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

A Phase 1 Study of BXCL701 in Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Myelodysplastic Syndrome With Excess Blasts - 2

This study is testing a new drug called BXCL701 to see if it can safely help people with relapsed or hard-to-treat Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dana-Farber Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05703542 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial aims to determine the safest and most effective dose of BXCL701, a synthetic dipeptide, for patients with refractory or relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome with Excess Blasts-2 (MDS-EB-2). The study will involve approximately 24 participants who will undergo screening, treatment, and follow-up evaluations, including blood collections and bone marrow biopsies. The trial is designed to assess the drug's safety and efficacy, as it has not yet been approved by the FDA for any condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome with Excess Blasts-2.

Not a fit: Patients who do not meet the eligibility criteria, such as those with less than 5% myeloblasts or those who have not undergone sufficient prior treatments, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of leukemia.

How similar studies have performed: While this approach is novel for BXCL701, similar studies targeting refractory AML have shown promise in the past.

Eligibility criteria

Inclusion Criteria:

* Age 18 and older
* Subjects with evidence of AML that meet at least one of the following criteria:

  * Relapsed AML: as evidence by ≥5% myeloblasts in the bone marrow, or reappearance of blasts in the peripheral blood
  * Refractory AML: ≤2 prior induction regimens (example: patients who receive 7 + 3 followed by 5 + 2 would count as one induction regimen) OR
  * Subjects with WHO defined myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) as defined by blast count between 10% - 19% in the bone marrow or peripheral blood blasts 5% - 19% or Auer rods noted and who are refractory or relapsed after at least 4 cycles of a hypomethylating agent (azacitidine, decitabine, or oral decitabine/cedazuridine)
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix B).
* Participants must have adequate organ and marrow function as defined below:

  * Estimated Creatinine Clearance ≥30 mL/min by Cockcroft-Gault calculation
  * Total Bilirubin ≤1.5 x ULN\*
  * ALT and AST ≤3x ULN\*
  * EF \>35%: \*unless considered due to leukemic organ involvement. NOTE: Subjects with Gilbert's Syndrome may have a total bilirubin \>1.5 x ULN per discussion with overall study PI.
* WBC \<25,000 / µL on day of 1 of cycle 1; cytoreduction is permitted with hydroxyurea which is allowed throughout cycle 1 until cycle 2 day 1
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants with treated central nervous system (CNS) disease are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial drug administration until 90 days after the last dose of study drug.
* Females of childbearing potential (i.e not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum pregnancy test performed within 7 days of day 1. Females must agree to refrain from unprotected sex/adequate contraception via barrier method from initial drug administration until 90 days after the last dose of study drug.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Subjects who have known Acute Promyelocytic Leukemia.
* Subjects with active CNS involvement with AML.
* Participants who have had chemotherapy, other investigational therapy, immunotherapy, or radiotherapy within 2 weeks or 5 half-lives from prior therapy, whichever is longer, prior to the first dose of study medication. Hydroxyurea is allowed with no required washout, and hydroxyurea may be administered for the first cycle of the protocol for patients who have proliferative disease (WBC \<25K) with a maximum allowed dose of 6 g per day.
* Participants who have received oral tyrosine kinase inhibitors (TKIs) within two weeks or 5 half-lives (whichever is longer) of the first dose of study medication
* Subjects who are \<100 days from allogeneic bone marrow transplant.
* Subjects who have active graft-versus host disease are not eligible. Patients should be off calcineurin inhibitors for at least 28 days (4 weeks) prior to start of study treatment C1D1
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \>Grade 1) with the exception of alopecia.
* Participants who are receiving any other investigational agents.
* Concomitant medications: It is strongly encouraged that patients who are on strong inducers or inhibitors of CYP3A4 be changed to a comparable drug if possible. If not possible, then dose reductions will need to be made as per APPENDIX C. Patients are not permitted to be on a gliptin (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin).
* Patients with a history of orthostatic hypotension with a baseline SBP \<100, or history of uncontrolled hypertension.
* Subject has cardiovascular disability status of NYHA class ≥2
* No concurrent active malignancies are allowed on study for ≥2 years prior to treatment start with the exception of currently treated basal cell or squamous cell carcinoma of the skin, carcinoma in-situ of the cervix or breast, or low-grade prostate cancer.
* Patients with known active hepatitis B virus (HBV) infection should be excluded because of potential effects on immune function and/or drug interactions. However, if a patient has HBV history with an undetectable HBV load by polymerase chain reaction (PCR), no liver-related complications, and is on definitive HBV therapy, then he/she would be eligible for study.
* Patients with known active hepatitis C virus (HCV) infection. Patients with a history of HCV infection who received definitive therapy and has an undetectable viral load by PCR would be eligible.
* Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results. As patients with AML and MDS are prone to infections, if patients are actively being treated with appropriate antibiotics or antifungal therapy with clinical evidence of infection control, then they will be considered eligible for study.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because BXCL701 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued.
* Inclusion of Women and Minorities: Both men and women of all races and ethnic groups are eligible for this trial.

Where this trial is running

Boston, Massachusetts

• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Eric S Winter, MD — Dana-Farber Cancer Institute
• Study coordinator: Eric S Winer, MD

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndrome With Excess Blasts-2; Myelodysplastic Syndrome with Excess Blasts-2; Refractory Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia