Testing GLB-001 for patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes

A First-in-human, Phase 1, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of GLB-001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes

This study is testing a new oral treatment called GLB-001 to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia or myelodysplastic syndromes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: GluBio Therapeutics Inc. (Industry-sponsored)
• Locations: 8 sites (Duarte, California and 7 other locations)
• Trial ID: NCT06146257 on ClinicalTrials.gov

What this trial studies

This clinical trial is a first-in-human, Phase 1, open-label study evaluating GLB-001 in patients with relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (R/R HR-MDS). The study consists of a dose escalation phase to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GLB-001 administered orally. Following the determination of the maximum tolerated dose, a dose expansion phase will further evaluate the drug's clinical activity and establish recommended doses for future studies. Approximately 42 participants will be enrolled across both phases.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory acute myeloid leukemia or higher-risk myelodysplastic syndromes who have failed or are ineligible for existing therapies.

Not a fit: Patients with early-stage leukemia or myelodysplastic syndromes who have not yet undergone treatment may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies have shown promise with similar dose escalation approaches in oncology, but this specific treatment is novel.

Eligibility criteria

Inclusion Criteria:

* Participants is ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
* Participants must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
* Participants are willing and able to adhere to the study visit schedule and other protocol requirements.
* Participants with histologically or cytologically confirmed AML including de novo AML or secondary AML transformed from MDS according to 2022 World Health Organization (WHO) criteria classification, or with histologically or cytologically confirmed HR-MDS.
* R/R AML and R/R HR-MDS who have failed or are ineligible for all available therapies which may provide clinical benefit.
* Participants must have the following screening laboratory values:

  * Total white blood cell count (WBC) \< 25 x 10\^9/L prior to the first dose of the study drug.
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN), unless considered due to extensive leukemic liver involvement, in which case AST and ALT can be ≤ 5.0 x ULN.
  * Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome, in which case serum total bilirubin \< 3 x ULN.
  * Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
  * International normalized ratio (INR) ≤ 1.5 x ULN and active partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
* Life expectancy ≥ 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
* Female Participants of child-bearing potential must have a negative serum or urine pregnancy test at screening and at pre-dose on Cycle 1 Day 1 (C1D1).

Exclusion Criteria:

* Participants with acute promyelocytic leukemia (APML).
* Participants with known leukemic involvement in central nervous system (CNS).
* Receipt of anticancer medications/therapies within 5 half-lives or 28 days before the first administration of the study drug.
* Participants with unresolved clinically significant non-hematologic toxicities of ≥ Grade 2 AE from prior therapies with exception of residual alopecia.
* Participants with chronic graft versus host disease (GVHD) requiring systemic immunosuppressive therapy.
* Participants with active malignancies other than AML or MDS.
* Participants who have undergone major surgery ≤ 4 weeks prior to the first dose of the study drug.
* Participants with immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection (bacterial and/or fungal), uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation.
* Participants with known chronic, active infection of hepatitis B virus (HBV), hepatitis C virus C (HCV), human immunodeficiency virus (HIV).
* Participants unable to swallow oral medications, or Participants with clinically significant diarrhea, vomiting or malabsorption felt limited absorption of orally administered medications.
* Participants with any other significant medical conditions, any other conditions, laboratory abnormality, or psychiatric illness which place the Participants at unacceptable risk if he/she were to participate in the study or that would hamper the Participants understanding of the study, or would prevent the Participant from complying with the study.
* Medications or supplements that are known to be strong and moderate inhibitors or inducers of CYP450 isozyme 3A4 (CYP3A4) and/or P-glycoprotein (P-gp), or strong inhibitors or inducers of CYP450 isozyme 2C8 (CYP2C8) within 14 days or 5 half-lives, whichever is shorter, before the first dose of study drug.
* Pregnant or lactating women.

Where this trial is running

Duarte, California and 7 other locations

• City of Hope Medical Center — Duarte, California, United States (Recruiting)
• University of California Irvine — Irvine, California, United States (Terminated)
• University of Kansas Medical Center Research Institute, Inc. — Kansas City, Kansas, United States (Recruiting)
• Alliance for Multispecialty Research, LLC — Merriam, Kansas, United States (Terminated)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (Terminated)
• Memorial Sloan Kettering Cancer Center-David H. Koch Center — New York, New York, United States (Terminated)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Terminated)

Study contacts

• Study coordinator: Kimberly Glen

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes