BST-236 + Venetoclax for Acute Myeloid Leukemia

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioSight Ltd.

Must not be taking: CYP3A inducers

Disqualifiers: Acute promyelocytic leukemia, MPN, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two treatments, BST-236 (Aspacytarabine) and venetoclax, for patients with Acute Myeloid Leukemia (AML) who cannot undergo standard chemotherapy. In the first part, researchers will determine the highest dose of the combination that patients can tolerate. In the second part, they will assess the treatment's effectiveness and safety. Eligible participants are adults with newly diagnosed AML who are unfit for typical treatments and have a manageable white blood cell count. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not use strong or moderate CYP3A inducers within 7 days before starting the study. It's best to discuss your current medications with the study team.

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

Research shows that combining BST-236 and venetoclax is generally safe for patients with Acute Myeloid Leukemia (AML) who cannot undergo intensive chemotherapy. Previous studies have found that BST-236, also known as aspacytarabine, is well-tolerated. For instance, one study found BST-236 safe when given alone to patients unable to have intensive treatment.

When combined with venetoclax, a drug already used for some blood cancers, the treatment remains manageable. Another study on this combination showed that patients handled the treatment well, with serious side effects being uncommon, allowing most patients to continue without major issues.

This trial will further investigate the safety of using BST-236 with venetoclax. However, early findings are promising, suggesting that the treatment is manageable for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of BST-236 and venetoclax for treating acute myeloid leukemia (AML) because it offers a novel approach that could enhance treatment outcomes. Unlike traditional chemotherapy, which broadly attacks dividing cells, BST-236 is a unique prodrug of cytarabine that may deliver higher concentrations of the active drug directly into leukemia cells with potentially fewer side effects. Venetoclax, on the other hand, targets the BCL-2 protein, which cancer cells often use to evade death, making it a powerful agent in prompting cancer cell apoptosis. Together, these treatments might improve the efficacy and safety profile compared to existing therapies, creating a promising option for AML patients.

What evidence suggests that this trial's treatments could be effective for Acute Myeloid Leukemia?

Research shows that the combination of BST-236 (also known as aspacytarabine) and venetoclax, which participants in this trial will receive, may be promising for treating acute myeloid leukemia (AML) in patients unable to undergo intensive chemotherapy. Studies have found that BST-236 alone is safe and effective as an initial treatment. In one study, aspacytarabine led to a complete response in 37% of patients with newly diagnosed AML. When combined with venetoclax, this treatment proved manageable and potentially effective. This suggests that the combination could be a valuable option for those who cannot undergo standard therapy. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults diagnosed with Acute Myeloid Leukemia (AML) who are unfit for standard chemotherapy can join this trial. They must have a WBC count of <25,000/μL, creatinine clearance ≥45 mL/min, liver enzymes ≤2.5 times the upper limit of normal, and an ECOG performance status score that fits the age criteria. Pregnant women or those treated previously for MDS with certain drugs cannot participate.

Inclusion Criteria

I cannot receive standard chemotherapy.

Creatinine clearance ≥45 mL/min

Total bilirubin ≤1.5 x ULN

Exclusion Criteria

I haven't taken strong or moderate CYP3A inducers in the last 7 days.

I haven't had surgery, except for minor procedures, in the last 14 days.

I have received treatment for acute myeloid leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 2 induction courses with BST-236 and venetoclax to determine the maximal tolerated dose

Up to 6 weeks

Maintenance Treatment

Responding patients receive up to 3 maintenance courses with BST-236 alone

Variable, up to several months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Post-study Follow-up

Participants are monitored for an additional year after the study

1 year

What Are the Treatments Tested in This Trial?

Interventions

• BST-236
• Venetoclax

Trial Overview The study is testing BST-236 combined with venetoclax to find out how safe and effective it is in treating AML patients who can't undergo standard therapy. The first part determines the highest dose patients can tolerate; the second part expands on this dose to further evaluate safety and effectiveness.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

BSR-236 + venetoclax

Who Is Running the Clinical Trial?

BioSight Ltd.

Lead Sponsor

Trials

4

Recruited

210+

Published Research Related to This Trial

Venetoclax is an oral medication with a favorable side-effect profile that shows promise in treating acute myeloid leukemia (AML), particularly for patients with refractory or relapsed cases.

This drug can serve as a bridge to hematopoietic cell transplant for curative treatment and may significantly extend survival for older patients who cannot tolerate more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid Leukemia Stem Cell? Pullarkat, VA., Newman, EM.[2021]

Venetoclax, a targeted oral agent, has significantly improved treatment outcomes for acute myeloid leukemia (AML), especially in older patients or those unable to undergo intensive chemotherapy, establishing a new standard of care when combined with hypomethylating agents or low-dose cytarabine.

The combination of venetoclax with other therapies, such as FLT-3 inhibitors and IDH inhibitors, is leading to better clinical results, marking a major advancement in AML treatment after decades of limited changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in acute myeloid leukemia - current and future directions. Lachowiez, C., DiNardo, CD., Konopleva, M.[2021]

In a study involving 15 Chinese patients with acute myeloid leukemia (AML) who could not tolerate intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a 38% reduction in the risk of death compared to placebo, with a median overall survival of 9.0 months versus 4.1 months for the placebo group.

The treatment resulted in a complete remission rate of 33% among those receiving venetoclax, while no patients in the placebo group achieved remission, indicating that venetoclax with LDAC is an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Venetoclax with low-dose cytarabine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: results from the Chinese cohort of a phase three randomized placebo-controlled trial]. Hu, Y., Jin, J., Zhang, Y., et al.[2021]

In a Phase 3 clinical trial, venetoclax combined with low-dose cytarabine showed improved response rates and overall survival in patients with newly diagnosed acute myeloid leukemia who couldn't undergo intensive chemotherapy, supporting its efficacy.

In an expanded access study in Japan involving 14 patients, the safety profile of venetoclax was consistent with previous findings, with neutropenia being the most common serious side effect, indicating that careful management of adverse events is crucial in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. Asada, N., Ando, J., Takada, S., et al.[2023]

In a study of 60 patients with high-risk MDS and AML, venetoclax demonstrated a 35% overall response rate, indicating its efficacy as a treatment option for these conditions.

However, the treatment was associated with significant hematologic toxicity, with 86.7% of patients experiencing grade 2 or higher side effects, and infections, particularly pneumonia, being the most common nonhematologic complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Real-life Turkish Experience of Venetoclax Treatment in High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia. Gemici, A., Ozkalemkas, F., Dogu, MH., et al.[2022]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax combined with hypomethylators and low-dose cytarabine has shown high response rates and improved overall survival in older, untreated patients with acute myeloid leukemia, based on preliminary data from small, uncontrolled studies.

The efficacy of venetoclax appears to stem from its ability to target leukemia stem cells by altering the metabolic environment, which is particularly effective in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? Pollyea, DA., Jordan, CT.[2020]

Venetoclax, an oral BCL-2 inhibitor, has shown promising efficacy in treating acute myeloid leukemia (AML) in elderly patients who cannot undergo intensive chemotherapy, with complete remission rates of 66.4% and 48% in phase III trials.

The introduction of venetoclax-based therapies has significantly improved treatment options for these patients, but further studies are needed to evaluate the long-term durability of responses and to explore its effectiveness compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer? Agarwal, S., Kowalski, A., Schiffer, M., et al.[2022]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

Venetoclax, a BCL-2 inhibitor, shows promising efficacy in treating acute myeloid leukemia (AML) in older patients, particularly those with poor prognosis and IDH mutations, while maintaining a favorable side-effect profile.

However, resistance to venetoclax can develop quickly when used alone, indicating that combining it with other therapies may be necessary to improve long-term treatment outcomes by overcoming resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy with a selective BCL-2 inhibitor in older patients with acute myeloid leukemia. Campos, EDV., Pinto, R.[2020]

Venetoclax, a BCL-2 inhibitor, shows promise in combination therapies for newly diagnosed or relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving high remission rates and deep molecular responses.

Despite these encouraging results, there are concerns about side effects such as incomplete blood count recovery and increased infection rates, particularly when used with chemotherapy, and more research is needed to understand the long-term effectiveness and durability of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. Shimony, S., Stone, RM., Stahl, M.[2023]

Venetoclax is an effective and well-tolerated treatment for advanced hematological malignancies, particularly in patients with chronic lymphocytic leukemia, showing a satisfactory overall event rate of 73%.

The most common adverse events associated with venetoclax include nausea, diarrhea, and thrombocytopenia, but these are generally mild and manageable, with few cases of severe complications like tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in Hematological Malignancy: A Systematic Review and Meta-Analysis of Clinical Trials. Li, Q., Cheng, L., Shen, K., et al.[2020]

In a study of 211 patients with untreated acute myeloid leukemia (AML) who were not eligible for intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a median overall survival of 8.4 months compared to 4.1 months for the placebo group, indicating a 30% reduction in the risk of death.

The treatment with venetoclax + LDAC also resulted in significantly higher complete response rates (48.3% vs. 13.2%) and improved event-free survival (4.9 months vs. 2.1 months), while maintaining a similar safety profile to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Wei, AH., Panayiotidis, P., Montesinos, P., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2923/502848/A-Phase-II-Study-of-Single-Agent-Aspacytarabine

A Phase II Study of Single Agent Aspacytarabine (BST-236) in ... A Phase II study of single agent Aspacytarabine (BST-236) in adults unfit for intensive chemotherapy with relapsed or refractory acute myeloid leukemia.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.7007

Efficacy and safety of aspacytarabine (BST-236) as a ... Aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123125699

Frontline Aspacytarabine with Venetoclax for Older/Unfit ... The combination induction regimen of ASPA and VEN followed by consolidation with ASPA alone, is a promising therapy. The regimen is tolerable.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10758705/

Aspacytarabine for the treatment of patients with AML unfit for ... In a phase 1/2 study conducted in patients with AML and acute lymphoblastic leukemia, aspacytarabine was found to be well-tolerated, with 6 g/m2 per day ...

5. targetedonc.com targetedonc.com/view/aspacytarabine-shows-promise-in-newly-diagnosed-acute-myeloid-leukemia

Aspacytarabine Shows Promise in Newly-Diagnosed ... Aspacytarabine for acute myeloid leukemia showed a complete response rate of 37% in phase 2 study.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04749355

Phase 2, Open-Label, Single Arm Study, With BST-236 in ... An open label multi center study to assess the safety and efficacy of BST-236 as single agent in adult patients unfit for standard therapy with Acute Myeloid ...