Lisaftoclax + Azacitidine for Myelodysplastic Syndrome

Recruiting at 1 trial location

Overseen By Qian Niu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: Other malignancies, Stem cell transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

464 Participants Needed

Trial Summary

What is the purpose of this trial?

A global multicenter, randomized, double-blind, placebo-controlled, pivotal phase III study. To evaluate overall survival (OS) of Lisaftoclax (APG-2575) combined with azacitidine (AZA) vs. placebo combined with azacitidine in newly diagnosed patients with HR-MDS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs that affect liver enzymes (CYP3A4) within 7 days before starting the trial.

What data supports the effectiveness of the drug combination Lisaftoclax + Azacitidine for Myelodysplastic Syndrome?

Research shows that a similar drug combination, venetoclax and azacitidine, has been effective in treating patients with myelodysplastic syndromes, especially after other treatments have failed. This combination has shown promising results in improving survival and achieving remission in patients. ^{1 2 3 4 5}

Is the combination of Lisaftoclax and Azacitidine safe for treating Myelodysplastic Syndrome?

While specific safety data for Lisaftoclax combined with Azacitidine is not available, studies on similar combinations like Venetoclax with Azacitidine show that they can cause side effects such as low blood cell counts and infections. These treatments have been used in other conditions, indicating they are generally safe but can have significant side effects. ^{1 2 3 4 6}

What makes the drug Lisaftoclax + Azacitidine unique for treating Myelodysplastic Syndrome?

Lisaftoclax + Azacitidine is unique because it combines a novel BCL-2 inhibitor (Lisaftoclax) with Azacitidine, which is a hypomethylating agent. This combination aims to enhance the effectiveness of treatment by targeting cancer cells more precisely, potentially offering a new option for patients who have not responded to standard therapies. ^{1 2 3 4 7}

Research Team

Xiaojun Huang, M.D., Ph.D.

Principal Investigator

Peking University People's Hospital

Guillermo Garcia-Manero, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for newly diagnosed patients with higher-risk Myelodysplastic Syndrome (HR-MDS), a condition that can lead to leukemia. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions or treatments.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My organs are functioning well.

I have been recently diagnosed with a high-risk form of MDS.

Exclusion Criteria

I do not have any ongoing infections that aren't under control.

I haven't taken strong drugs that affect liver enzymes in the last week.

Any condition that the subject is deemed inappropriate for study participation after evaluation by the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lisaftoclax (APG-2575) combined with azacitidine or placebo combined with azacitidine

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Azacitidine
• Lisaftoclax (APG-2575)

Trial Overview The study is testing the effectiveness of Lisaftoclax (APG-2575) combined with Azacitidine (AZA) compared to a placebo combined with AZA in improving overall survival rates in HR-MDS patients. It's a phase III trial, meaning it's late-stage research involving more participants to confirm effectiveness and monitor side effects.

Participant Groups

Group I: Lisaftoclax (APG-2575) combined with Azacitidine Experimental Treatment 2 Interventions

Group II: Placebo combined with Azacitidine Active Control 2 Interventions

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?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Findings from Research

In a phase 1b study involving 44 patients with relapsed/refractory higher-risk myelodysplastic syndromes (MDS), the combination of venetoclax and azacitidine demonstrated significant activity, with a median overall survival of 12.6 months after prior treatment failure with hypomethylating agents.

The treatment resulted in hematological improvements, including complete remission in 7% of patients and transfusion independence in 36%, indicating that venetoclax plus azacitidine can provide meaningful clinical benefits for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Zeidan, AM., Borate, U., Pollyea, DA., et al.[2023]

In a study involving 21 patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML), the combination of venetoclax and azacitidine (5-AZA) was shown to effectively target malignant cells even after failure of hypomethylating agents (HMA).

Importantly, this combination therapy demonstrated the ability to spare healthy hematopoiesis, which is crucial for maintaining blood cell production and reducing toxicity in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with azacitidine targets refractory MDS but spares healthy hematopoiesis at tailored dose. Jilg, S., Hauch, RT., Kauschinger, J., et al.[2020]

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 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]

The combination of azacitidine and venetoclax is safe and well-tolerated in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia, with a recommended phase 2 dose established as azacitidine 75 mg/m2 for 5 days plus venetoclax 400 mg for 14 days.

The treatment showed a high overall response rate of 87% among the 23 enrolled patients, indicating promising preliminary activity for this combination therapy in treatment-naive and relapsed or refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Bazinet, A., Darbaniyan, F., Jabbour, E., et al.[2022]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

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]

References

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

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. [2023]

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

Venetoclax with azacitidine targets refractory MDS but spares healthy hematopoiesis at tailored dose. [2020]

3. United States 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. [2023]

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

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]

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

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

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

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