GLB-001 for Acute Myeloid Leukemia

Recruiting at 4 trial locations

Overseen By Kimberly Glen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GluBio Therapeutics Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: APML, CNS involvement, active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called GLB-001 for individuals with relapsed or stubborn acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS), where the cancer has returned or resisted other treatments. The main goal is to assess the safety and tolerability of GLB-001 and determine the best dose for future studies. The trial consists of two parts: initially, it examines how the drug behaves in the body and its early effects, then it expands to confirm safety at different doses. Individuals who have exhausted all other available treatments for AML or HR-MDS without success might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial, especially if they are strong or moderate inhibitors or inducers of specific enzymes (CYP3A4, CYP2C8) or P-glycoprotein. This should be done within 14 days or 5 half-lives of the medication, whichever is shorter, before starting the study drug.

Is there any evidence suggesting that GLB-001 is likely to be safe for humans?

Research on GLB-001 remains in the early stages, so detailed safety information is limited. Initial findings suggest that researchers are testing this treatment to assess its safety and tolerability. The current study is a first-in-human trial, marking the first time GLB-001 is tested in people.

This phase focuses on understanding how the body processes the drug and its effects. Early trials like this aim to find the right dose that patients can handle without serious side effects. The study seeks to determine the maximum dose patients can safely take.

Since GLB-001 is not yet approved for any condition, this trial is crucial for establishing its safety. Researchers closely monitor participants to quickly manage any potential side effects. While data on GLB-001 is still emerging, the ongoing trial is a key step in determining its safety for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia (AML), which often involve chemotherapy or targeted therapies like FLT3 inhibitors, GLB-001 offers a unique approach by being administered orally, potentially simplifying the treatment process for patients. Researchers are particularly excited about GLB-001 because it targets specific pathways in leukemia cells, aiming to improve effectiveness while reducing side effects. Additionally, the dose escalation and expansion design aims to find the optimal dose that balances safety and efficacy, a crucial step that might lead to better outcomes compared to current options.

What evidence suggests that GLB-001 might be an effective treatment for acute myeloid leukemia?

Research has shown that GLB-001 may benefit patients with relapsed or hard-to-treat acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS). In this trial, participants will receive GLB-001 as a monotherapy in two phases: dose escalation and dose expansion. Early studies suggest it might help some patients achieve complete remission, where cancer cells are reduced to undetectable levels. GLB-001 targets specific processes that aid cancer cell growth, potentially controlling or reducing the disease. Although these findings are preliminary, they offer hope that GLB-001 could effectively treat these challenging conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Gang Lu, Ph.D.

Principal Investigator

GluBio Therapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (HR-MDS). They must have failed or be ineligible for other treatments and meet specific health criteria like blood counts, liver and kidney function. Pregnant women are excluded.

Inclusion Criteria

My blood tests and health status meet the study's requirements.

You need to understand and agree to sign a document before any study-related tests or procedures are done.

I have been diagnosed with AML or HR-MDS according to WHO criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1a: Evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GLB-001 to determine the maximum tolerated dose or maximum administered dose.

Up to 28 days after first dose

Dose Expansion

Phase 1b: Confirm tolerability of selected doses and evaluate efficacy to identify minimally active dose and select recommended dose for phase 2.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• GLB-001

Trial Overview GLB-001, an oral medication, is being tested in this Phase 1 study on patients with certain types of blood cancers. The study has two parts: dose escalation to assess safety and dosage levels, followed by dose expansion to find the most effective yet tolerable dose for future studies.

How Is the Trial Designed?

Group I: Dose Expansion of GLB-001 as a Monotherapy in Participants with R/R AML and R/R HR-MDS-Phase 1b Experimental Treatment 1 Intervention

Part 1b (Dose Expansion) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R AML and R/R HR-MDS participants.

Group II: Dose Escalation of GLB-001 as a Monotherapy in Participants with R/R AML and R/R HR-MDS-Phase 1a Experimental Treatment 1 Intervention

Part 1a (Dose Escalation) of the study will enroll R/R AML and R/R HR-MDS participants and will evaluate the safety, tolerability, PK, PD and preliminary efficacy of GLB-001 administered orally, and determine the maximum tolerated dose/maximum administered dose (MTD/MAD) in R/R AML or R/R HR-MDS patients who are eligible for dose limiting toxicity (DLT) evaluation.

Who Is Running the Clinical Trial?

GluBio Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

Glasdegib, an oral Hedgehog pathway inhibitor, significantly improves survival rates in patients with untreated acute myeloid leukemia (AML) when combined with low-dose cytarabine compared to low-dose cytarabine alone.

The BRIGHT AML 1019 trial is a Phase III study evaluating glasdegib in combination with standard chemotherapy regimens, focusing on overall survival and other important outcomes in adults with untreated AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Cortes, JE., Dombret, H., Merchant, A., et al.[2020]

In the phase 2 BRIGHT AML 1003 trial, patients with acute myeloid leukemia who received glasdegib combined with low-dose cytarabine (LDAC) had a significantly higher complete remission rate of 19.2% compared to 2.6% for those receiving LDAC alone, indicating enhanced efficacy of the combination treatment.

Even in patients who did not achieve complete remission, the addition of glasdegib improved overall survival by 37% and led to better recovery of blood cell counts, suggesting that glasdegib provides clinical benefits beyond just achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy. Cortes, JE., Heidel, FH., Fiedler, W., et al.[2021]

In a study of 42 adult AML patients, researchers found that the Hedgehog (Hh) pathway, particularly the GLI1 protein, is overexpressed in patients with refractory/relapse AML, leading to decreased drug sensitivity.

Inhibiting GLI1 alone was shown to enhance the sensitivity of AML cells to treatment, suggesting that targeting GLI1 could be a promising strategy for improving outcomes in AML without the added risks associated with combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the PI3K/AKT pathway via GLI1 inhibition enhanced the drug sensitivity of acute myeloid leukemia cells. Liang, H., Zheng, QL., Fang, P., et al.[2022]

Glasdegib is an effective treatment for acute myelogenous leukemia (AML), particularly in high-risk patients such as the elderly and those with relapsed or refractory disease, showing good tolerability when combined with standard chemotherapy or low-intensity treatments.

In 2018, glasdegib received FDA approval for use with low-dose cytarabine specifically for newly diagnosed AML patients over 75 years old or those with significant health issues, highlighting its role in improving treatment options for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of glasdegib for the treatment of acute myelogenous leukemia. Thomas, X., Heiblig, M.[2020]

Overexpression of the GLI1 gene in acute myeloid leukemia (AML) cells promotes cell growth and reduces sensitivity to chemotherapy, indicating that targeting GLI1 could improve treatment outcomes.

Inhibiting GLI1 with GANT61, along with using the CDK4/6 inhibitor PD 0332991, showed synergistic effects in enhancing chemotherapy sensitivity, suggesting a potential new therapeutic strategy for patients with relapsed or refractory AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia. Zhou, C., Du, J., Zhao, L., et al.[2021]

Recent advancements in understanding the genetic changes in acute myeloid leukemia (AML) have not yet translated into significant new treatments, highlighting a gap in therapeutic progress despite improved biological insights.

Current chemotherapy regimens can induce remission in AML patients, but most experience relapse within months, underscoring the urgent need for novel targeted therapies that could enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is targeted therapy feasible in acute myelogenous leukemia? Konig, H., Levis, M.[2021]

In a study of 46 newly diagnosed acute myeloid leukemia (AML) patients, GLI-1 was found to be overexpressed in bone marrow samples, particularly in patients with poor risk categories, indicating its potential role as a prognostic marker.

Higher levels of GLI-1 mRNA were associated with a lack of complete remission after chemotherapy, suggesting that GLI-1 overexpression could be a novel therapeutic target for improving outcomes in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients. El Zaiat, RS., Nabil, R., Khalifa, KA., et al.[2023]

Recent advancements in the treatment of acute myeloid leukemia (AML) have led to a cure rate of about 20% for patients, thanks to new drug developments and improved supportive care, such as the use of broad-spectrum antibiotics.

The identification of specific leukemic syndromes that respond well to targeted interventions marks a significant breakthrough, paving the way for future therapies that could be tailored to the unique molecular characteristics of different leukemia types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interpreting data in AML. Wiernik, PH.[2013]

This case report describes the first known instance of acute myeloid leukemia M6 presenting with a skeletal lesion, specifically an osteolytic lesion in the right humerus of a 17-year-old boy.

The patient was treated with induction and consolidation chemotherapy, highlighting the potential for effective treatment even in rare presentations of AML M6.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteolytic Bone Lesions - A Rare Presentation of AML M6. Geetha, N., Sreelesh, KP., Priya, MJ., et al.[2020]

Glasdegib, a small-molecule inhibitor targeting the hedgehog pathway, was approved by the FDA for treating newly diagnosed acute myeloid leukemia (AML) in patients over 75 or those unable to undergo intensive chemotherapy, showing significant promise in improving patient outcomes.

In a phase II trial, the combination of glasdegib with low-dose cytarabine (LDAC) nearly doubled the median overall survival of patients compared to LDAC alone, highlighting its efficacy in a vulnerable patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy. Goldsmith, SR., Lovell, AR., Schroeder, MA.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06146257

A Study of GLB-001 in Patients With Relapsed or ... Apparent clearance. Up to 2 years. Complete Remission Without Minimal Residual Disease (CRMRD-) Rate in Participants with Acute Myeloid Leukemia (AML), CRMRD- ...

2. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00150562

A First-in-Human FIH, Phase 1, Multicenter, Open-label, ... A first-in-human FIH, Phase 1, multicenter, open-label, dose escalation and expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10199

A Study of GLB-001 in Patients With Relapsed or ... GLB-001-01 is a first-in-human (FIH), Phase 1, open-label, dose escalation and expansion clinical study of GLB-001 in participants with relapsed or refractory ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/478841

A Study of GLB-001 in Patients With Myeloid Malignancies Study GLB-001-02 is a phase 1, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06378437

A Study of GLB-001 in Patients With Myeloid Malignancies Study GLB-001-02 is a phase 1, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary ...

6. trialx.com trialx.com/clinical-trials/listings/243640/a-study-of-glb-001-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-or-relapsed-or-refractory-higher-risk-myelodysplastic-syndromes/?&radius=50

A Study of GLB-001 in Patients With Relapsed or ... Study GLB-001-01 is a first-in-human (FIH), Phase 1, open-label, dose escalation and expansion clinical study of GLB-001 in participants with ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/437395

A Study of GLB-001 in Patients With Relapsed or Refractory ... The dose escalation part (Phase 1a) of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and ...