BH-30236 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 9 trial locations

Overseen By Sponsor Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BlossomHill Therapeutics

Must not be taking: CLK inhibitors

Disqualifiers: Acute promyelocytic leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

74 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot have unresolved adverse effects from prior therapies or require systemic therapy for graft versus host disease within 4 weeks before starting the study drug. It's best to discuss your specific medications with the trial team.

What data supports the idea that the drug BH-30236 for Acute Myeloid Leukemia and Myelodysplastic Syndrome is an effective treatment?

The available research does not provide specific data on the effectiveness of BH-30236 for Acute Myeloid Leukemia and Myelodysplastic Syndrome. Instead, it discusses other drugs and therapies for these conditions, such as venetoclax, midostaurin, and gilteritinib, which have been approved for use. These alternatives have shown effectiveness in treating Acute Myeloid Leukemia by targeting specific genetic mutations or proteins in cancer cells. However, there is no direct mention of BH-30236 in the context of these conditions. ^{1 2 3 4 5}

What safety data is available for BH-30236 in AML and MDS treatment?

The provided research does not contain specific safety data for BH-30236 in the treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The studies mention BH3 mimetics and other treatments but do not directly address BH-30236. Further investigation into clinical trial databases or specific studies on BH-30236 would be necessary to find relevant safety data. ^{1 3 6 7 8}

Is the drug BH-30236 a promising treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome?

The drug BH-30236, also known as a BH3 mimetic, is promising because similar drugs have shown potential in targeting cancer cells by promoting cell death in leukemia. This approach could improve treatment outcomes for patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome. ^{1 9 10 11 12}

What is the purpose of this trial?

Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/refractory acute myelogenous leukemia (R/R AML) or higher-risk myelodysplastic syndrome (HR-MDS). Phase 1 (Dose Escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered orally. Approximately 50 participants may be enrolled in Phase 1 of the study. Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study. The dose expansion part (Phase 1b) will be followed to understand the relationships among dose, exposure, toxicity, tolerability and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

Research Team

Sponsor Contact

Principal Investigator

BlossomHill Therapeutics, Inc.

Eligibility Criteria

This trial is for people who have acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) that has come back or didn't respond to treatment. The study will involve about 74 participants in total.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I have relapsed AML or high-risk MDS with more than 5% bone marrow blasts.

I have had between 1 to 5 treatments for my condition.

Exclusion Criteria

I have been treated with a CLK inhibitor before.

I have no other active cancers, with some exceptions.

I haven't needed strong medication for graft versus host disease in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of BH-30236 to evaluate safety, tolerability, and determine the recommended dose for expansion

28 days per cycle

Multiple visits per cycle for dose administration and monitoring

Dose Expansion

Participants receive BH-30236 at selected recommended doses to further evaluate safety and anti-leukemic activity

28 days per cycle, up to 1 year

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BH-30236

Trial Overview The trial is testing BH-30236, a new oral medication. It's divided into two phases: Phase 1 tests safety and how the body reacts to different doses, while Phase 1b looks at how well it works and its effects at specific doses.

Participant Groups

Group I: Dose Expansion Cohort Experimental Treatment 1 Intervention

BH-30236 administered at a dose(s) determined form the data of dose escalation cohort

Group II: Dose Escalation Cohort Experimental Treatment 1 Intervention

BH-30236 monotherapy for Dose Escalation

Who Is Running the Clinical Trial?

BlossomHill Therapeutics

Lead Sponsor

Trials

2

Recruited

340+

Findings from Research

The small-molecule BH3-mimetic ABT-737 significantly enhances the effectiveness of daunorubicin (DNR) in treating acute myeloid leukemia (AML) cell lines, showing lower IC50 values when used in combination, indicating a synergistic effect.

The combination treatment not only increased cell death through enhanced apoptosis but also provided greater growth inhibition compared to using DNR alone, suggesting a potential strategy to overcome chemoresistance in leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines. Dariushnejad, H., Zarghami, N., Rahmati, M., et al.[2021]

Since 2017, the FDA has approved nine new agents for treating acute myeloid leukaemia, including targeted therapies like venetoclax and various inhibitors, which provide new options for patients.

Some of these approved treatments are single-agent therapies or specific combinations, which may limit their overall effectiveness, highlighting the need for ongoing research into better combinations of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing the benefits of available targeted therapies in acute myeloid leukaemia. Kantarjian, H., Short, NJ., DiNardo, C., et al.[2022]

FLT3 inhibitors have shown promise in targeting specific mutations in acute myeloid leukemia (AML), potentially improving treatment outcomes for patients with these mutations.

IDH inhibitors and other drugs may offer significant benefits for patients with secondary AML, highlighting the need for tailored therapeutic approaches in this challenging subtype of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapeutics in Acute Myeloid Leukemia. DiNardo, CD., Stone, RM., Medeiros, BC.[2022]

Recent genome sequencing has identified specific genetic mutations in acute myeloid leukemia (AML) cells, which are crucial for developing targeted therapies.

Current clinical studies are exploring various molecular targeting therapies for AML, including FLT3 inhibitors, PLK1 inhibitors, IDH2 inhibitors, and XPO1 inhibitors, aimed at directly addressing these genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Progress in molecularly targeted therapies for acute myeloid leukemia]. Tomita, A.[2015]

The overall survival rate for younger patients with newly diagnosed acute myeloid leukemia has tripled over the past 20 years, largely due to advancements in supportive care and tailored treatment strategies based on individual risk factors.

Despite achieving complete remission in 50%-70% of newly diagnosed patients, only about 25% remain disease-free, highlighting the need for ongoing development of novel agents and targeted therapies, especially for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing therapy for acute myeloid leukemia. Kohrt, HE., Coutre, SE.[2019]

In a post-marketing surveillance study of 173 patients with del 5q-MDS treated with lenalidomide, 78% experienced adverse drug reactions, with the most common being thrombocytopenia (46.2%) and neutropenia (42.2%).

Despite the high rate of adverse reactions, lenalidomide demonstrated efficacy, with 34.2% of transfusion-dependent patients achieving transfusion independence, and no new safety concerns or increased risk of acute myeloid leukemia progression were identified during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide treatment of Japanese patients with myelodysplastic syndromes with 5q deletion: a post-marketing surveillance study. Uno, S., Motegi, Y., Minehata, K., et al.[2023]

The study presents a new protocol to model acquired resistance to BH3 mimetics in patient-derived xenograft (PDX) mouse models of acute myeloid leukemia, which is crucial for understanding treatment limitations.

A dynamic BH3 profiling (DBP) method is introduced to identify effective drug therapies by measuring drug-induced apoptosis signaling, providing a potential strategy to overcome resistance to BH3 mimetics in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic BH3 profiling method for rapid identification of active therapy in BH3 mimetics resistant xenograft mouse models. Olesinski, EA., Bhatt, S.[2022]

The BH3 mimetic S1 effectively induces apoptosis in human primary acute myeloid leukemia (AML) cells, with varying sensitivity among 27 samples classified into sensitive, intermediate, and resistant groups based on their IC(50) values.

Combining S1 with the MEK/ERK inhibitor PD98059 significantly enhances the apoptotic effect in drug-resistant AML cells by reducing phosphorylated BCL-2 levels and promoting the dissociation of BCL-2 heterodimers, suggesting a potential strategy to overcome resistance in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Relationship between BH3 mimetic S1 and expression of BCL-2 family members in acute myeloid leukemia]. Wang, XB., Shi, M., Mu, LJ., et al.[2018]

In a study of 415 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), certain subtypes (AML-MRC-M and AML-MRC-H) showed better overall survival rates compared to other subtypes, indicating that not all AML-MRC patients are high-risk.

Intensive therapy significantly improved overall survival and event-free survival in patients with AML-MRC-M and AML-MRC-H, suggesting that tailored treatment approaches based on specific subgroups can enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy. Montalban-Bravo, G., Kanagal-Shamanna, R., Class, CA., et al.[2023]

The WHO's 2002 classification change allowed for the diagnosis of low-blast count acute myeloid leukemia (LBC-AML) with 20-30% bone marrow blasts, which is more common in elderly patients and those with therapy-related conditions, and has a clinical course similar to myelodysplastic syndromes (MDS).

Hypomethylating agents like azacitidine and decitabine have been effective in treating both MDS and LBC-AML, showing potential to improve survival, especially in patients with poor-risk cytogenetics, and current research is exploring combinations with immune checkpoint inhibitors to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Low-Blast Count AML using Hypomethylating Agents. De Bellis, E., Fianchi, L., Buccisano, F., et al.[2020]

The traditional classification of acute myeloid leukemia (AML) is inadequate for predicting treatment outcomes and does not account for significant subgroups, such as elderly patients or those with AML following myelodysplastic syndrome (MDS).

A new classification model divides AML into MDS-related (MDR-AML) and true de novo (TDN-AML) groups, which have distinct genetic characteristics and treatment responses, suggesting that this revised model could improve therapeutic strategies and outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revised classification of acute myeloid leukemia. Head, DR.[2013]

The combination of the BH3 mimetic ABT-263 and the MEK1/2 inhibitor pimasertib (MEKI) significantly increased apoptosis in acute myeloid leukemia (AML) cells while sparing normal bone marrow cells, suggesting a targeted approach to treatment.

This synergistic effect was confirmed in both AML cell lines and primary cells, as well as in a mouse model, indicating that this combination therapy could be a promising strategy to enhance AML treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic cooperation between ABT-263 and MEK1/2 inhibitor: effect on apoptosis and proliferation of acute myeloid leukemia cells. Airiau, K., Prouzet-Mauléon, V., Rousseau, B., et al.[2018]

References

1. Iran pubmed.ncbi.nlm.nih.gov

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Harnessing the benefits of available targeted therapies in acute myeloid leukaemia. [2022]

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

Novel Therapeutics in Acute Myeloid Leukemia. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Progress in molecularly targeted therapies for acute myeloid leukemia]. [2015]

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

Optimizing therapy for acute myeloid leukemia. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Lenalidomide treatment of Japanese patients with myelodysplastic syndromes with 5q deletion: a post-marketing surveillance study. [2023]

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

Dynamic BH3 profiling method for rapid identification of active therapy in BH3 mimetics resistant xenograft mouse models. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Relationship between BH3 mimetic S1 and expression of BCL-2 family members in acute myeloid leukemia]. [2018]

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

Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Treatment of Low-Blast Count AML using Hypomethylating Agents. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Revised classification of acute myeloid leukemia. [2013]

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

Synergistic cooperation between ABT-263 and MEK1/2 inhibitor: effect on apoptosis and proliferation of acute myeloid leukemia cells. [2018]