Cusatuzumab + Background Therapy for Acute Myeloid Leukemia

(ELEVATE Trial)

Not currently recruiting at 29 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OncoVerity, Inc.

Must not be taking: Live vaccines

Disqualifiers: CNS leukemia, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 28-day cycles, up to 42 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment combination for acute myeloid leukemia (AML), a type of blood cancer. The study evaluates a mix of medicines: cusatuzumab (an experimental treatment), venetoclax, and azacitidine, to assess their effectiveness and potential side effects. People diagnosed with AML who cannot receive intense chemotherapy are suitable candidates for this trial. The trial aims to provide new treatment options for those facing this challenging condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but certain treatments like emergency leukapheresis, hydroxyurea, and cytarabine must be stopped at least 24 hours before starting the study drug.

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

Research has shown that the combination of cusatuzumab, venetoclax, and azacitidine is generally well-tolerated by older adults with acute myeloid leukemia (AML). Earlier studies suggest that most patients can handle these drugs without major problems, though side effects may occur.

The combination of cusatuzumab and venetoclax has demonstrated promising safety results, with patients often managing the treatment well. Adding azacitidine does not significantly alter the safety profile. Azacitidine and venetoclax are already used together in AML treatments and are considered safe, though patients might experience common side effects like nausea or low blood counts.

Overall, these treatment combinations appear safe for most people, based on past research. However, anyone considering joining a trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cusatuzumab with Venetoclax and Azacitidine for treating Acute Myeloid Leukemia because it introduces a unique approach that differs from standard chemotherapy. Cusatuzumab is an antibody that targets CD70, a protein found on leukemia cells, potentially offering a more precise attack on cancerous cells compared to traditional treatments. Additionally, this combination leverages Venetoclax, which disrupts cancer cell survival processes, and Azacitidine, which affects DNA methylation, providing a multi-pronged strategy to tackle leukemia. This innovative blend of mechanisms could lead to more effective treatments and improved outcomes for patients.

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

Research shows that using cusatuzumab and venetoclax together can fight leukemia stem cells more effectively than using each drug alone. This combination enhances the effectiveness of each drug. In this trial, some participants will receive cusatuzumab and venetoclax. Studies have found that patients treated with venetoclax and azacitidine, a common treatment for acute myeloid leukemia (AML), typically live less than 15 months on average. Another group in this trial will receive a combination of cusatuzumab, venetoclax, and azacitidine, which might improve outcomes for people with AML. This approach aims to offer a treatment option without chemotherapy, focusing on attacking cancer cells while protecting the rest of the body. ^{1 2 5 6 7}

Who Is on the Research Team?

Clayton Smith, MD

Principal Investigator

OncoVerity, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with a new or secondary type of acute myeloid leukemia (AML) who haven't been treated yet, except to manage high white blood cell counts. They should be fairly active and not eligible for intensive chemo or stem cell transplant at the start. People with HIV, central nervous system leukemia, allergies to the drugs being tested, or recent live vaccines can't join.

Inclusion Criteria

I cannot undergo intensive chemotherapy.

My condition is acute myeloid leukemia (AML), either newly diagnosed or after a previous cancer.

I have been diagnosed with acute myeloid leukemia, not including acute promyelocytic leukemia.

Exclusion Criteria

I am eligible for a stem cell transplant from a donor.

I am HIV positive.

My leukemia has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cusatuzumab in combination with venetoclax and azacitidine for the treatment of acute myeloid leukemia

28-day cycles, up to 42 months

Visits on Day 1, Day 3, and Day 17 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 42 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Cusatuzumab
• Venetoclax

Trial Overview The study tests cusatuzumab combined with other AML treatments like venetoclax and azacitidine. It aims to understand how safe this combination is and how well patients tolerate it.

How Is the Trial Designed?

Group I: Experimental: Cohort 2: Cusatuzumab + Venetoclax Experimental Treatment 2 Interventions

Participants enrolled in this cohort will receive venetoclax ramp-up to 400 mg orally (as background therapy) starting on Cycle 1 Day 1 and followed by 400 mg daily dosing starting on Cycle 1 Day 4 plus cusatuzumab IV on Day 3 and Day 17 of each 28-day cycle. Cohort 2 will not be enrolled in the US.

Group II: Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) Experimental Treatment 3 Interventions

Participants enrolled at US sites will receive cusatuzumab 10 mg/kg and potentially escalate to 20 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). Participants enrolled from ex-US sites will receive cusatuzumab 20 mg/kg and potentially de-escalate to 10 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies).

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

OncoVerity, Inc.

Lead Sponsor

Trials

6

Recruited

430+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

argenx

Industry Sponsor

Trials

76

Recruited

11,500+

Tim Van Hauwermeiren

argenx

Chief Executive Officer since 2008

B.Sc. and M.Sc. in Bioengineering from Ghent University, Executive MBA from The Vlerick School of Management

Dr. Peter Ulrichts

argenx

Chief Medical Officer since 2023

MD from Maastricht University, PhD in Molecular Immunology from Maastricht University

Published Research Related to This Trial

In a study of 60 patients with acute myeloid leukemia (AML), the combination of venetoclax and azacitidine (Ven+AZA) demonstrated a high response rate, with 70.8% of previously untreated patients unfit for standard chemotherapy achieving complete remission (CR) or CR with incomplete hematological recovery (CRi) after one cycle.

Ven+AZA was found to be safe and tolerable, with some patients achieving minimal residual disease (MRD) negativity, particularly in those with favorable genetic mutations like NPM1, IDH1/IDH2, and TP53, indicating its potential effectiveness in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. Yu, WJ., Jia, JS., Wang, 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 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]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., 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]

The combination of venetoclax, azacitidine, and homoharringtonine (VAH) resulted in a high composite complete remission rate of 70.8% in patients with relapsed or refractory acute myeloid leukemia (R/R AML), indicating strong efficacy of this treatment regimen.

Patients treated with VAH had a median overall survival of 22.1 months and a 1-year overall survival rate of 61.5%, suggesting that this regimen not only effectively induces remission but also improves survival outcomes in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial. Jin, H., Zhang, Y., Yu, S., et al.[2023]

In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.

The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. Drozd-Sokołowska, J., Mądry, K., Barankiewicz, J., et al.[2023]

In a study of 35 patients with relapsed or refractory acute myeloid leukaemia (R/R AML) treated with venetoclax-azacitidine (VEN-AZA), the complete remission rate was significantly higher at 48.6% compared to 15% in a historical cohort treated with azacitidine (AZA).

Patients receiving VEN-AZA also showed a trend towards longer overall survival (12.8 months) compared to those treated with AZA (7.3 months), indicating that VEN-AZA may offer a more effective treatment option for R/R AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine-venetoclax versus azacitidine salvage treatment for primary induction failure or first relapsed acute myeloid leukaemia patients. Petit, C., Saillard, C., Mohty, B., et al.[2023]

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a study of 57 elderly patients (average age 69.9 years) with acute myeloid leukemia, the combination of venetoclax and azacitidine (VEN + AZA) showed a high overall response rate of 87.5% and a complete remission (CR) rate of 68.8%, indicating strong efficacy in this population.

The treatment was associated with a median overall survival (OS) of 11.5 months, and achieving minimal residual disease (MRD) negativity (<0.1%) was more common with VEN + AZA compared to traditional chemotherapy, although older patients (≥75 years) and those with higher ECOG scores faced more challenges in achieving MRD negativity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. Yu, H., Wang, C., Lei, Y., et al.[2023]

In a study of 6 children with refractory or relapsed acute myeloid leukemia (AML), the combination of venetoclax, azacitidine, and cladribine (VAC regimen) resulted in significant treatment responses, with 4 achieving complete remission and 1 showing partial remission.

Despite severe side effects like grade IV neutropenia and thrombocytopenia, there were no treatment-related deaths or infections, indicating that the VAC regimen is both effective and safe for this vulnerable patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. DU, WW., Liu, SX., Wang, Y., et al.[2023]

Citations

1. 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 ...

2. 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 ...

3. 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.

4. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3918/424011/The-Combination-of-the-BCL-2-Antagonist-Venetoclax

The Combination of the BCL-2 Antagonist Venetoclax with the ... Overall, these results indicate that a combination of cusatuzumab with venetoclax eliminates LSCs synergistically and more efficiently than as ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12350645/

Comprehensive view on chemotherapy-free management ... Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04150887

Study Details | NCT04150887 | Cusatuzumab in ... The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia ( ...

7. 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 ... Among responders, 47% were MRD negative (Roboz et al, Blood 2021, 138: 369). Overall, the study results showed promising efficacy and safety and support the ...