Venetoclax, Azacitidine, and Cusatuzumab for Acute Myeloid Leukemia

Recruiting at 35 trial locations

Overseen By OncoVerity OncoVerity

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OncoVerity, Inc.

Must not be taking: Immune suppressants, Live vaccines

Disqualifiers: Prior AML treatment, CNS leukemia, Active infections, 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: 1

Duration: 28-day cycles, repeated

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immune suppressive agents within 4 weeks before starting the trial, and you must be free of systemic corticosteroids for more than 5 days before the first administration of cusatuzumab, except for physiologic replacement doses.

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

Research shows that combining Venetoclax and Azacitidine can lead to longer survival and quick, lasting remissions in patients with Acute Myeloid Leukemia who can't undergo intensive chemotherapy. Additionally, Cusatuzumab combined with Azacitidine has shown initial positive results in treating this condition, suggesting potential effectiveness when all three are used together. ^{1 2 3 4 5}

Is the combination of Venetoclax, Azacitidine, and Cusatuzumab safe for humans?

The combination of Cusatuzumab and Azacitidine has been generally well tolerated in studies, with common side effects including infections and blood-related issues. No severe dose-limiting toxicities were observed, and further research is ongoing to explore its safety with Venetoclax. ^{1 2 3 5 6}

What makes the drug combination of venetoclax, azacitidine, and cusatuzumab unique for treating acute myeloid leukemia?

This drug combination is unique because it includes cusatuzumab, a novel anti-CD70 monoclonal antibody, which is being investigated for its potential to enhance the effects of azacitidine and venetoclax in patients who are not eligible for intensive chemotherapy. Cusatuzumab targets a specific protein (CD70) on leukemia cells, which may help improve treatment outcomes. ^{2 4 5 6 7}

Eligibility Criteria

This trial is for adults with newly diagnosed AML who can't have intensive therapy. They must understand the study and agree to participate, not have had certain treatments before joining, be at least 75 years old or have a performance status of 2 or 3 if younger, and meet specific health criteria related to heart, lung function, kidney clearance, and liver function.

Inclusion Criteria

I have been diagnosed with AML, not related to MDS with 10-19% blasts.

Women of childbearing potential must have a negative pregnancy test and agree to contraception measures

Must sign an informed consent form (ICF) indicating understanding of the study purpose and procedures and willingness to participate

Exclusion Criteria

I have been treated with specific drugs for my blood disorder.

Known allergies, hypersensitivity, or intolerance to specific medications

Conditions where participation may not be in the participant's best interest

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cusatuzumab in combination with venetoclax and azacitidine or venetoclax and azacitidine alone

28-day cycles, repeated

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular visits (in-person)

Treatment Details

Interventions

• Cusatuzumab

Trial Overview The trial tests if adding cusatuzumab to venetoclax and azacitidine improves survival in AML patients ineligible for chemotherapy. It compares this combination against the standard treatment of venetoclax and azacitidine alone.

Participant Groups

Group I: Cusatuzumab in combination with venetoclax and azacitidine Experimental Treatment 3 Interventions

Cusatuzumab 20 mg/kg administered intravenously on days 3 and 17 in combination with venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Group II: Venetoclax in combination with azacitidine Active Control 2 Interventions

Venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Who Is Running the Clinical Trial?

OncoVerity, Inc.

Lead Sponsor

Trials

6

Recruited

430+

Findings from Research

In a pooled analysis of treatment-naïve patients with FLT3-mutant acute myeloid leukemia, the combination of venetoclax and azacitidine resulted in a significantly higher composite complete remission rate (67%) compared to azacitidine alone (36%), with a median overall survival of 12.5 months versus 8.6 months.

The treatment was found to be safe, with no unexpected toxicities reported, indicating that venetoclax + azacitidine is a promising option for older patients or those with comorbidities who are ineligible for intensive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. Konopleva, M., Thirman, MJ., Pratz, KW., et al.[2023]

In a phase 2 study involving 103 patients with untreated acute myeloid leukaemia, the combination of cusatuzumab at a dose of 20 mg/kg with azacitidine resulted in a higher complete remission rate of 27% compared to 12% for the 10 mg/kg dose, suggesting that 20 mg/kg is the optimal dose for future trials.

Safety profiles were similar between the two doses, with common severe adverse events including thrombocytopenia and anaemia, indicating that while the treatment can have serious side effects, the higher dose may offer better efficacy without significantly increasing risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. Pabst, T., Papayannidis, C., Demirkan, F., et al.[2023]

In treatment-naïve patients with IDH1/2-mutant acute myeloid leukemia (AML), the combination of venetoclax and azacitidine resulted in a high composite complete remission rate of 79% and a median overall survival of 24.5 months, significantly outperforming the azacitidine-only group, which had an 11% remission rate and 6.2 months of survival.

The treatment was found to be safe, with no unexpected toxicities reported, and the favorable outcomes for patients with IDH1/2 mutations were consistent regardless of their cytogenetic risk, indicating a robust efficacy of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Pollyea, DA., DiNardo, CD., Arellano, ML., et al.[2023]

The study evaluates the safety and efficacy of venetoclax combined with oral azacitidine as maintenance therapy for patients with acute myeloid leukemia (AML) who are in complete remission but have incomplete blood count recovery after intensive treatment.

The primary goal of the trial is to assess relapse-free survival, with secondary outcomes including overall survival and quality of life, highlighting the potential of this combination therapy to prevent relapse in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the VIALE-M phase III trial of venetoclax and oral azacitidine maintenance therapy in acute myeloid leukemia. Ivanov, V., Yeh, SP., Mayer, J., et al.[2022]

In a phase 1 study involving 6 Japanese participants with newly diagnosed acute myeloid leukemia, the combination of cusatuzumab and azacitidine was found to be generally well tolerated, with no dose-limiting toxicities observed.

The most common treatment-emergent adverse events were leukopenia in 66.7% of participants and constipation in 50.0%, indicating that while side effects occurred, they were manageable and did not prevent further investigation of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment. Ikezoe, T., Usuki, K., Aida, K., et al.[2023]

Cusatuzumab, an anti-CD70 monoclonal antibody, combined with azacitidine showed preliminary efficacy in treating newly diagnosed acute myeloid leukemia (AML) in patients who are not eligible for intensive chemotherapy, with 19 out of 38 patients achieving an objective response.

The treatment was generally well tolerated, with the most common side effects being infections (84.2%) and hematologic toxicities (78.9%), indicating a manageable safety profile as the study progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. Pabst, T., Vey, N., Adès, L., et al.[2023]

The combination of venetoclax (Ven) and azacitidine (AZA) shows a high efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), with an overall complete response rate of 57.9% across 19 studies involving 1615 patients.

This treatment is particularly effective for newly diagnosed AML patients, achieving a complete response rate of 67.5%, although it is less effective for those with relapsed or refractory AML, which had a response rate of only 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. Du, Y., Li, C., Yan, J.[2023]

References

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

Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. [2023]

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

Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. [2023]

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

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. [2023]

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

Design of the VIALE-M phase III trial of venetoclax and oral azacitidine maintenance therapy in acute myeloid leukemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. [2023]

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

The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. [2023]