GLB-001 for Acute Myeloid Leukemia

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: GluBio Therapeutics Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: APML, CNS involvement, active infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, GLB-001, in patients with certain types of blood cancer that haven't responded to other treatments. The goal is to find out how safe the drug is and what dose works best.

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.

What data supports the effectiveness of the drug GLB-001 for treating acute myeloid leukemia?

Research shows that inhibiting GLI1, a gene involved in the Hedgehog signaling pathway, can make acute myeloid leukemia cells more sensitive to drugs. This suggests that targeting GLI1, which GLB-001 may do, could be a promising strategy for treating this type of leukemia. ^{1 2 3 4 5}

What safety data exists for GLB-001 (glasdegib) in humans?

Glasdegib has been studied in combination with low-dose cytarabine for acute myeloid leukemia, and it was generally well-tolerated in clinical trials, leading to its FDA approval for certain patients. However, there are concerns about side effects when combined with other treatments, as it may affect blood-forming cells. ^{1 4 6 7 8}

How does the drug GLB-001 differ from other treatments for acute myeloid leukemia?

GLB-001 may involve targeting the Hedgehog signaling pathway, similar to glasdegib, which is a known treatment for AML that works by inhibiting this pathway to improve survival in patients unsuitable for intensive chemotherapy. This approach is unique as it focuses on a specific molecular target, potentially offering a novel strategy for enhancing drug sensitivity in AML treatment. ^{1 2 6 9 10}

Research Team

Gang Lu, Ph.D.

Principal Investigator

GluBio Therapeutics Inc.

Eligibility Criteria

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.

I am 18 years or older and can sign the consent form.

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

Trial Timeline

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

Treatment Details

Interventions

• GLB-001 (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Targeting the PI3K/AKT pathway via GLI1 inhibition enhanced the drug sensitivity of acute myeloid leukemia cells. [2022]

2. India pubmed.ncbi.nlm.nih.gov

High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients. [2023]

3. England pubmed.ncbi.nlm.nih.gov

GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia. [2021]

4. England 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Is targeted therapy feasible in acute myelogenous leukemia? [2021]

6. England pubmed.ncbi.nlm.nih.gov

Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. [2020]

7. Italy pubmed.ncbi.nlm.nih.gov

Osteolytic Bone Lesions - A Rare Presentation of AML M6. [2020]

8. Spain 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. [2019]

9. England pubmed.ncbi.nlm.nih.gov

An evaluation of glasdegib for the treatment of acute myelogenous leukemia. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Interpreting data in AML. [2013]