Venetoclax, Azacitidine, and Cusatuzumab for Acute Myeloid Leukemia

Recruiting at 39 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the experimental drug cusatuzumab to the existing treatment of venetoclax and azacitidine extends the lives of people with acute myeloid leukemia (AML). AML is a type of blood cancer, and the existing drugs are typically used when traditional chemotherapy isn't an option. Participants will receive either the combination with cusatuzumab or the standard treatment to compare effectiveness. The trial seeks individuals diagnosed with AML who have not received prior treatment for it. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the combination of cusatuzumab, venetoclax, and azacitidine is generally safe for patients. A previous study with older patients who had untreated acute myeloid leukemia (AML) found no major safety problems with this drug combination. Most patients managed the treatment without serious side effects.

Venetoclax and azacitidine are already used to treat AML, especially for those who can't undergo chemotherapy, and past studies have shown they have a good safety record. Adding cusatuzumab did not significantly increase negative effects.

While this trial is still in a phase where the safety of cusatuzumab is being tested, the evidence so far suggests it can be used without major concerns. Patients should always consult a healthcare provider to understand what these findings mean for their personal situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Researchers are excited about these treatments because Cusatuzumab offers a novel approach to tackling acute myeloid leukemia (AML). Unlike the standard of care, which typically involves chemotherapy drugs like cytarabine and daunorubicin, Cusatuzumab targets CD70, a protein involved in cancer cell survival. This mechanism is different from traditional chemotherapy, potentially offering a more precise attack on cancer cells. Additionally, when combined with venetoclax and azacitidine, Cusatuzumab could enhance the overall effectiveness against AML, providing hope for improved outcomes.

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

This trial will compare two treatment approaches for acute myeloid leukemia (AML). One arm will test the combination of venetoclax and azacitidine with cusatuzumab. Studies have shown that this combination might improve outcomes for people with AML, with half of the patients achieving a complete response (CR) or a complete response with incomplete blood count recovery (CRi). The other arm will test the standard treatment of venetoclax and azacitidine alone, which typically results in less than 15 months of survival. Adding cusatuzumab may enhance treatment by targeting specific proteins on leukemia cells, potentially leading to better survival rates. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

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

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

Exclusion Criteria

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

I do not have any active cancer other than the one specified.

Known allergies, hypersensitivity, or intolerance to specific medications

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1504.2/529435/Trial-in-Progress-A-Multicenter-Open-Label

Trial in Progress: A Multicenter, Open Label, Randomized ... A multicenter, open label, randomized, phase 2 study of Venetoclax and Azacitidine Plus Cusatuzumab versus Venetoclax and Azacitidine alone in newly diagnosed ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649712102365X

Safety and Efficacy of Cusatuzumab in Combination with ... Results: Based on data through Jul 9, 2021, 44 patients enrolled with median age 75 years (range 32-89), 36.4% had secondary AML, 40.9% had an ECOG performance ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10316251/

Results from a phase I/II trial of cusatuzumab combined with ... Despite this changing landscape, overall survival (OS) is <15 months with venetoclax/azacitidine, and even in the subgroup of responding patients, median ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06384261

NCT06384261 | A Study Comparing Venetoclax and ... A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy.

5. haematologica.org haematologica.org/article/view/haematol.2022.281563

Results from a phase I/II trial of cusatuzumab combined ... All responding patients achieved CR or CRi (no partial remission or morphologic leukemia-free state): 14 (36.8%) with CR and five (13.2%) with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12422247/

Efficacy of Venetoclax Combined with Azacitidine in Elderly ... In our ≥ 65-year relapsed AML cohort treated with venetoclax plus azacitidine, we observed an ORR of 60% (CR 40%, CRi 20%) with median OS 9.2 ...