BP1001 + Venetoclax + Decitabine for Acute Myeloid Leukemia

Recruiting at 5 trial locations

Overseen By Maro Ohanian

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bio-Path Holdings, Inc.

Must be taking: Venetoclax, Decitabine

Disqualifiers: Active infection, Hepatitis, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 26 weeks

108 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objectives of this study are to assess: (1) whether the combination of BP1001 plus venetoclax plus decitabine provides greater efficacy (Complete Remission \[CR\], Complete Remission with incomplete hematologic recovery \[CRi\], Complete Remission with partial hematologic recovery \[CRh\], than venetoclax plus decitabine alone (by historical comparison) in participants with untreated AML that cannot or elect not to be treated with more intensive chemotherapy; (2) whether BP1001-based treatment provides greater efficacy (CR, CRi, CRh) than intensive chemotherapy (by historical comparison) in participants with refractory/relapsed AML.

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 have received any anti-cancer therapy within 14 days before starting the trial, except for certain medications like hydroxyurea. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination BP1001, Venetoclax, and Decitabine for treating Acute Myeloid Leukemia?

Research shows that combining Venetoclax with Decitabine is effective for older patients with acute myeloid leukemia (AML), with a significant number achieving complete remission. In one study, patients receiving Venetoclax and Decitabine had longer overall survival and higher response rates compared to those receiving Decitabine alone. ^{1 2 3 4 5}

Is the combination of BP1001, Venetoclax, and Decitabine safe for humans?

The combination of Venetoclax and Decitabine has been studied in elderly patients with acute myeloid leukemia (AML) and is generally well tolerated. Common side effects include nausea, diarrhea, constipation, fatigue, and low white blood cell count, but no severe tumor lysis syndrome (a condition where cancer cells break down rapidly) was observed. ^{1 2 3 4 5}

What makes the drug combination of BP1001, Venetoclax, and Decitabine unique for treating acute myeloid leukemia?

This drug combination is unique because it includes BP1001, which is not commonly used in standard treatments for acute myeloid leukemia (AML). Venetoclax and Decitabine are already used together for older patients or those unfit for intensive chemotherapy, but the addition of BP1001 could potentially enhance the treatment's effectiveness, especially in high-risk AML patients. ^{1 4 6 7 8}

Research Team

Maro Ohanian, DO

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with untreated Acute Myeloid Leukemia (AML) or relapsed/refractory AML, who can't or choose not to undergo intensive chemotherapy. Participants must have proper liver and kidney function, an ECOG performance status of 0-2, and agree to use contraception. Excluded are those with active leptomeningeal leukemia, recent anti-cancer therapy, potential pregnancy/breastfeeding during the study period, significant concurrent illnesses or infections.

Inclusion Criteria

Participant's WBC count is 25 x 10^9/L or less at study initiation

I can take care of myself and am up and about more than half of my waking hours.

Willing and able to provide written informed consent

Exclusion Criteria

I have leukemia in the fluid around my brain and need spinal injections.

Presence of concurrent conditions that may compromise the participant's ability to tolerate study treatment

I have not had a heart attack, stroke, or similar event in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BP1001 in combination with Venetoclax plus Decitabine. The treatment is divided into three cohorts: untreated AML, refractory/relapsed AML, and refractory/relapsed AML with venetoclax intolerance or resistance.

Approximately 26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of overall survival, event-free survival, and duration of response.

180 days

Extension

Potential continuation of treatment for cohorts that show promising results after initial evaluation.

Long-term

Treatment Details

Interventions

• BP1001
• Decitabine
• Venetoclax

Trial Overview The trial is testing BP1001 in combination with venetoclax plus decitabine against historical data for efficacy in achieving complete remission in AML patients. It aims to determine if this new treatment combo is more effective than existing treatments for those who cannot receive intensive chemotherapy.

Participant Groups

Group I: Untreated AML Experimental Treatment 1 Intervention

BP1001 in combination with Ventoclax plus decitabine

Group II: Refractory/Relapsed AML (ventoclax-intolerant or resistant) Experimental Treatment 1 Intervention

BP1001 + decitabine combination in patients who are resistant or intolerant of venetoclax-based treatment, or considered not optimal candidates for a venetoclax-based therapy.

Group III: Refractory/Relapsed AML Experimental Treatment 1 Intervention

BP1001 in combination with Ventoclax plus decitabine

Who Is Running the Clinical Trial?

Bio-Path Holdings, Inc.

Lead Sponsor

Trials

6

Recruited

300+

Findings from Research

In a study involving 145 older patients (median age 74) with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, the combination of venetoclax with decitabine or azacitidine resulted in a high complete remission (CR) rate of 67%, demonstrating its efficacy in this challenging population.

The treatment was well tolerated, with no cases of tumor lysis syndrome reported, and the median overall survival was 17.5 months, indicating that venetoclax combined with hypomethylating agents is a promising option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. DiNardo, CD., Pratz, K., Pullarkat, V., et al.[2021]

In a study comparing older adults with newly diagnosed acute myeloid leukemia (AML), those treated with the combination of decitabine (DEC) and venetoclax (VEN) had a significantly longer median overall survival of 13.4 months compared to 8.3 months for those receiving DEC alone.

The combination therapy also resulted in a higher response rate of 70.3% versus 24.3% for DEC monotherapy, indicating that DEC+VEN is more effective in treating AML without increasing short-term mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. Kwag, D., Cho, BS., Bang, SY., et al.[2022]

In a study of 22 heavily pre-treated patients with relapsed or refractory acute myeloid leukaemia (RR-AML), the combination of venetoclax and decitabine resulted in a 45.5% overall response rate, with 40.9% achieving complete remission, demonstrating its efficacy in a real-world setting.

While the treatment was effective, it was associated with significant side effects, including grade IV neutropenia and thrombocytopenia in all patients, but no deaths were attributed to the treatment side effects, indicating that the adverse effects were manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. Tong, J., Zhao, N., Hu, X., et al.[2022]

In a phase 2 trial involving 168 patients with acute myeloid leukaemia (AML), the combination of venetoclax and a 10-day regimen of decitabine resulted in a high overall response rate of 74%, with particularly impressive results in newly diagnosed AML patients (89%).

The treatment demonstrated a manageable safety profile, with common adverse events including neutropenia and infections, and a 30-day mortality rate of only 3.6%, indicating that this combination therapy is both effective and relatively safe for older patients or those unfit for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. DiNardo, CD., Maiti, A., Rausch, CR., et al.[2021]

A once-weekly low-dose decitabine (LDDec) combined with venetoclax (VEN) showed high efficacy in treating elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving an overall response rate of 88% for AML and 64% for MDS in a retrospective study of 39 patients.

Patients receiving the LDDec/VEN regimen experienced longer treatment durations and a trend towards higher transfusion independence compared to those on standard dosing, suggesting that this approach may reduce severe myelosuppression while maintaining effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. Levitz, D., Saunthararajah, Y., Fedorov, K., et al.[2023]

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]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In a study of 81 patients with acute myeloid leukemia (AML) receiving venetoclax with decitabine or azacitidine, 72.8% experienced infections, with the most common pathogens being Candida albicans and Klebsiella pneumonia.

The study found that the incidence of infectious complications was lower with this treatment compared to conventional chemotherapy, and high leukemia burden and fever were identified as significant risk factors for developing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. Zhu, LX., Chen, RR., Wang, LL., et al.[2022]

References

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

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. [2021]

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

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. [2022]

4. England pubmed.ncbi.nlm.nih.gov

10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. [2021]

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

A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. [2023]

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

Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. [2022]