BXCL701 Phase 1 R/R Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT05703542 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-379
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to find the safest and most effective dose of the study drug, BXCL701, for the treatment of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). The names of the study drugs involved in this study are/is:

• BXCL701

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome With Excess Blasts-2

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Defined as the highest dose at which fewer than one-third of patients experience a dose-level toxicity (DLT). MTD will be used to inform recommended Phase II dose. If no DLTs are observed, the MTD is not reached.

  From initiation of therapy to day 28, up to 35 days

• Number of Participants with treatment related Adverse Events per CTCAE 5.0

  Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  4 weeks up to 1 year

Secondary Outcomes (8)

• Complete Remission (CR) Rate

  Disease assesment at baseline, cycle 1, 3 , 8, 15 , 22, and day 1 of every cycle and up to 12 cycles, corresponding to a treatment duration up to one year (each cycle is 28 days).

• Complete Response with Incomplete Count Recovery (CRi) Rate

  Disease assesment at baseline, cycle 1, 3 , 8, 15 , 22, and day 1 of every cycle and up to 12 cycles, corresponding to a treatment duration up to one year (each cycle is 28 days).

• Partial Response (PR) Rate

  Disease assesment at baseline, cycle 1, 3 , 8, 15 , 22, and day 1 of every cycle and up to 12 cycles, corresponding to a treatment duration up to one year (each cycle is 28 days)..

• Morphologic Leukemia-free State (MLFS) Rate

  Disease assesment at baseline, cycle 1, 3 , 8, 15 , 22, and day 1 of every cycle and up to 12 cycles, corresponding to a treatment duration up to one year (each cycle is 28 days).

• Hematologic Improvement (HI) Rate

  Disease assesment at baseline, cycle 1, 3 , 8, 15 , 22, and day 1 of every cycle and up to 12 cycles, corresponding to a treatment duration up to one year (each cycle is 28 days).

Study Arms (1)

Dose Escalation BXCL701

EXPERIMENTAL

Dose escalation will occur using a 3+3 dose escalation approach, evaluating 4 different dose levels of BXCL701. During each 28 day study cycle participants will take BXCL701 2x daily for up to 12 cycles.

Drug: BXCL701

Interventions

BXCL701 DRUG

Tablet, taken Orally

Also known as: Talabostat

Dose Escalation BXCL701

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eric Stephen Winer, MD: lead

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

PT-100 dipeptide; talabostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Eric S Winter, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric S Winer, MD

CONTACT

1 617-632-2053; erics_winer@dfci.harvard.edu

Eric S Winter, MD

CONTACT

1 617-632-2053; erics_winer@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2022
• First Posted: January 30, 2023
• Study Start: February 2, 2023
• Primary Completion: March 17, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)