Motixafortide for MRD Sensitization in AML

Official title

A Pilot Clinical Trial of Motixafortide for Measurable Residual Disease (MRD) Sensitization in Acute Myeloid Leukemia (AML)

Overview

This is a pilot phase I study evaluating the effect of motixafortide on determination of measurable residual disease (MRD) level in patients with acute myeloid leukemia (AML) who have completed induction treatment. Consenting and eligible patients will undergo standard of care (SOC) bone marrow and peripheral blood assessments with SOC MRD assays, followed by a single injection of motixafortide. Ten to 14 hours after injection, the patient will undergo peripheral blood collection for the same applicable MRD tests

Interventions

• Drug Motixafortide
  Motixafortide is a CXCR4 inhibitor for the mobilization of hematopoietic stem progenitor cells (HSPCs) in patients undergoing autologous stem cell transplantation. It is provided as a single subcutaneous injection.

Primary outcome measures

• Efficacy of motixafortide on measurable residual disease (MRD) levels [Time frame: Day 1 before motixafortide and Day 2 (estimated total time is 2 days)]

Secondary outcome measures (7)

• Proportion of patients changing from negative to positive MRD levels [Time frame: Day 1 before motixafortide and Day 2 (estimated total time is 2 days)]
• Percentage change in variant allele frequency (VAF) levels by next-generation sequencing (NGS) using error-corrected sequencing (MRD-Seq) [Time frame: Day 1 before motixafortide and Day 2 (estimated total time is 2 days)]
• Percentage change in VAF levels by NGS using MRD-Seq between bone marrow and peripheral blood assessments [Time frame: Day 1 before motixafortide and Day 2 (estimated total time is 2 days)]
• Percentage change in detectable transcript levels by polymerase chain reaction (PCR) [Time frame: Day 1 before motixafortide and Day 2 (estimated total time is 2 days)]
• Relapse-free survival (RFS) [Time frame: From Day 1 through completion of follow-up (estimated total time is 18 months)]
• Time to next line of therapy [Time frame: From Day 1 through completion of follow-up (estimated total time is 18 months)]
• Overall survival (OS) [Time frame: From Day 1 through completion of follow-up (estimated total time is 18 months)]

Eligibility criteria

Inclusion criteria

• Diagnosed with acute myeloid leukemia (AML), excluding APL, treated with 1-2 cycles of front-line chemotherapy.
• Achieved CBC parameters compatible with complete remission as defined by ELN 2022.
• Planning to undergo a standard of care blood draw and bone marrow assessment with SOC MRD assays, including morphology, flow cytometry for MRD, NGS panels for MRD, and PCR tests for MRD as applicable.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Life expectancy > 3 months.
• Adequate organ function as defined below:

• Total bilirubin ≤ 2.0 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 5.0 x IULN
• Creatinine clearance > 30 mL/min by Cockcroft-Gault
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion criteria

• Evidence of more than 5% blasts in in the peripheral blood by manual differential within 5 days prior to study enrollment.
• Prior history of allogeneic stem cell transplant.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to motixafortide.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Identifiers

NCT: NCT07392970 · 202603045

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗