Venetoclax, Azacitidine, and Cusatuzumab for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: OncoVerity, Inc.

Must not be taking: Immune suppressants, Live vaccines

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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

Trial 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 (Monoclonal Antibodies)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California Los Angeles Los Angeles, CA

University of Colorado Health - Anschutz Cancer Pavilion - Anschutz Medical Campus Aurora, CO

Advent Health Orlando, FL

Banner MD Anderson Gilbert, AZ

More Trial Locations

Who Is Running the Clinical Trial?

OncoVerity, Inc. Lead Sponsor

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] To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia.

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] Cusatuzumab, a high-affinity anti-CD70 antibody, has shown preliminary activity as a treatment for acute myeloid leukaemia when combined with azacitidine. We aimed to determine the optimum dose for future trials of cusatuzumab in combination with azacitidine in patients with previously untreated acute myeloid leukaemia who are not eligible for intensive chemotherapy.

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] To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

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] Prevention of relapse is a major therapeutic challenge and an unmet need for patients with acute myeloid leukemia (AML). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis in AML cells. When combined with azacitidine, it leads to prolonged overall survival and rapid, durable remissions in treatment-naive AML patients ineligible for intensive chemotherapy. VIALE-M is a randomized, double-blind, two-arm study to evaluate the safety and efficacy of venetoclax in combination with oral azacitidine (CC-486) as maintenance therapy in patients in complete remission with incomplete blood count recovery after intensive induction and consolidation therapies. The primary end point is relapse-free survival. Secondary outcomes include overall survival, minimal residual disease conversion and improvement in quality-of-life. Trial Registration Number: NCT04102020 (ClinicalTrials.gov).

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

Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment. [2023] We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti-CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single-arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14. Subsequently, cusatuzumab was administered intravenously on days 3 and 17 at 20 mg/kg in combination with azacitidine (75 mg/m2 ) on days 1-7 of each 28-day cycle. All six participants had at least one treatment-emergent adverse event, and the most common treatment-emergent adverse events (all grades) were leukopenia (four participants [66.7%]) and constipation (three participants [50.0%]). No dose-limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants, and further exploration of this combination is warranted.

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] Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in acute myeloid leukemia (AML). This two-part, open-label, multicenter, phase I/II trial evaluated cusatuzumab plus azacitidine in patients with newly diagnosed AML ineligible for intensive chemotherapy. Patients received a single dose of cusatuzumab at one of four dose levels (1, 3, 10, or 20 mg/kg) 14 days before starting combination therapy. In phase I dose escalation, cusatuzumab was then administered on days 3 and 17, in combination with azacitidine (75 mg/m2) on days 1-7, every 28 days. The primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. The primary objective in phase II was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients were enrolled: 12 in phase I (three per dose level; four with European LeukemiaNet 2017 adverse risk) and 26 in phase II (21 with adverse risk). An objective response (≥partial remission) was achieved by 19/38 patients (including 8/26 in phase II); 14/38 achieved complete remission. Eleven patients (37.9%) achieved an objective response among the 29 patients in phase I and phase II treated at the RP2D. At a median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. The most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Seven patients (18.4%) reported infusion-related reactions, including two with grade 3 events. Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing.

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] The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).