BH-30236 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 12 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

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BH-30236 for individuals with challenging blood conditions, specifically relapsed or refractory acute myelogenous leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). The trial consists of different parts: one tests BH-30236 alone, and another combines it with a drug called venetoclax. The goal is to assess the safety and effectiveness of BH-30236, both independently and in combination. Individuals with AML or HR-MDS who have tried 1-5 other treatments without success might be suitable candidates. As a Phase 1 trial, this research aims to understand how BH-30236 works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BH-30236 is under investigation for safety and tolerability in individuals with relapsed or hard-to-treat acute myelogenous leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). As this is the first human trial of BH-30236, specific safety information remains limited.

The trial is in its early stages, focusing primarily on safety. Researchers are beginning to assess how well participants tolerate the treatment. Participants receive varying doses to determine manageable levels and to monitor for side effects.

BH-30236 is also being tested in combination with venetoclax, a drug already approved for certain blood cancers. Venetoclax's established safety profile aids in understanding its safety when used alongside BH-30236.

Overall, as an early-phase study, the primary objective is to identify safe dosage levels and monitor for side effects. Participants are closely observed to ensure their safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BH-30236 for treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) because it represents a novel approach compared to existing treatments like chemotherapy or targeted therapies such as Venetoclax. Unlike these standard treatments, BH-30236 is being explored both as a standalone therapy and in combination with Venetoclax, potentially enhancing its effectiveness. This combination could improve patient outcomes by synergistically targeting cancer cells more effectively. Additionally, the dose escalation and expansion strategy aims to identify the optimal therapeutic dose, which can maximize efficacy while minimizing side effects.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia and myelodysplastic syndrome?

Research has shown that BH-30236 is a promising new treatment for certain types of blood cancer, specifically relapsed/refractory acute myelogenous leukemia (R/R AML) and higher-risk myelodysplastic syndrome (HR-MDS). This trial includes separate treatment arms to evaluate BH-30236 as a monotherapy and in combination with venetoclax. BH-30236 blocks proteins that help cancer cells grow and survive. Early results suggest that BH-30236 may reduce the number of cancer cells. When combined with venetoclax, a drug that already combats some blood cancers, BH-30236 might be even more effective. Although the data remains early, these findings offer hope for people facing these challenging conditions. ^{3 6 7 8 9}

Who Is on the Research Team?

Sponsor Contact

Principal Investigator

BlossomHill Therapeutics, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Dose Expansion Cohort - Monotherapy Experimental Treatment 1 Intervention

BH-30236 based on Monotherapy dose escalation data.

Group II: Dose Expansion Cohort - Combination with Venetoclax Experimental Treatment 2 Interventions

BH-30236 in Combination with Venetoclax based on Dose Escalation data

Group III: Dose Escalation Cohort - Monotherapy Experimental Treatment 1 Intervention

BH-30236 Monotherapy for Dose Escalation

Group IV: Dose Escalation Cohort - Combination with Venetoclax Experimental Treatment 2 Interventions

BH-30236 in Combination with Venetoclax for Dose Escalation.

Who Is Running the Clinical Trial?

BlossomHill Therapeutics

Lead Sponsor

Trials

2

Recruited

340+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06501196

NCT06501196 | A Study of BH-30236 in Relapsed ... 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 ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/514775

A Study of BH-30236 in Relapsed/ Refractory Acute ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124086361

BH-30236, a Novel Macrocyclic Clk Inhibitor Modulating ... A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-leukemic activity of BH-30236 in ...

4. bhtherapeutics.com bhtherapeutics.com/press-releases/blossomhill-therapeutics-to-present-at-the-67th-american-society-of-hematology-ash-annual-meeting-on-design-of-phase-1-1b-study-of-bh-30236-an-oral-macrocyclic-clk-inhibitor-in-r-r-aml-or-hr-mds/

BlossomHill Therapeutics to Present at the 67th American ... BH-30236 is currently being evaluated as a monotherapy or in combination with venetoclax in a first-in-human, Phase 1/1b dose escalation study ...

5. trial.medpath.com trial.medpath.com/clinical-trial/b45ac28109c6d1c2/safety-tolerability-pharmacokinetics-anti-leukemic-activity-orally-available-clk-inhibitor

A Study of BH-30236 in Relapsed/ Refractory Acute ... - MedPath 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06501196

NCT06501196 | A Study of BH-30236 in Relapsed ... This is a Phase 1/1b, multi-center, open-label, dose escalation, first-in-human study to evaluate the safety, tolerability, PK, PD, and preliminary anti- ...

7. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15219.a-study-of-bh-30236-in-relapsed-refractory-acute-myelogenous-leukemia-and-higher-risk-myelodysplastic-syndrome.html

A Study of BH-30236 in Relapsed/? Refractory Acute ... Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/ ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5998/527608/A-Phase-1-1b-Open-Label-Dose-Escalation-First-in

A Phase 1/1b Open-Label, Dose Escalation, First-in-Human ... This first-in-human trial evaluates BH-30236 in patients with previously treated AML or higher risk MDS. Study Design and Methods: Patients ≥18 years with ...

9. careacross.com careacross.com/clinical-trials/trial/NCT06501196

A Study of BH-30236 in Relapsed/ Refractory Acute ... Phase 1b Dose Expansion will enroll approximately 24 subjects to evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 at ...