Q702 + Azacitidine + Venetoclax for Acute Myeloid Leukemia

Overseen By Abhishek Maiti, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: CNS leukemia, Liver disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 cycles (16 weeks)

32 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn about the safety and tolerability of the drug combination of Q702, azacitidine, and venetoclax when given to participants with relapsed/refractory AML.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions a 'washout period' (time without taking certain medications) of 2 weeks or 5 half-lives for prior therapies before starting the trial treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Q702, Azacitidine, and Venetoclax for treating Acute Myeloid Leukemia?

Research shows that the combination of venetoclax and azacitidine improves remission rates and survival in older or unfit patients with acute myeloid leukemia compared to azacitidine alone. This suggests that adding venetoclax to azacitidine can be effective for treating this condition. ^{1 2 3 4 5}

Is the combination of Q702, Azacitidine, and Venetoclax safe for treating acute myeloid leukemia?

The combination of Venetoclax and Azacitidine has been studied in patients with acute myeloid leukemia and is generally considered to have acceptable safety, especially in those who are older or unfit for standard chemotherapy. While specific safety data for Q702 in this combination is not provided, the existing studies suggest that the Venetoclax and Azacitidine combination is tolerable. ^{1 3 4 6 7}

What makes the drug combination of Q702, Azacitidine, and Venetoclax unique for treating acute myeloid leukemia?

The combination of Q702 with Azacitidine and Venetoclax is unique because it adds a novel component, Q702, to the existing regimen of Azacitidine and Venetoclax, which is already used for older or unfit patients with acute myeloid leukemia to improve remission rates and survival. This new combination may offer additional benefits, although specific data on Q702's impact in this context is not yet available. ^{1 2 3 4 6}

Research Team

Abhishek Maiti, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people with Acute Myeloid Leukemia (AML) that has come back or hasn't responded to treatment. Participants should meet specific health conditions, but the exact inclusion and exclusion criteria are not provided.

Inclusion Criteria

I have been diagnosed with AML or MDS/AML with 10-19% blasts.

I am taking a low dose of steroids, no more than 10 mg of prednisone or its equivalent.

My liver is working well.

Exclusion Criteria

I have an active hepatitis B or C, or HIV/HTLV-1 infection.

I have an ongoing infection that hasn't improved with treatment.

Participants under legal protection measure (guardianship, trusteeship or safeguard of justice) and/or uncontrolled psychiatric comorbidities, ongoing illicit substance abuse, any impairment or unwillingness to comply with the treatments, follow-up, requirements and procedures of this clinical trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Q702, azacitidine, and venetoclax in cycles of 28 days, with blood samples and bone marrow aspirations collected

4 cycles (16 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and relapse-free survival

Up to 1 year

Treatment Details

Interventions

• Azacitidine
• Q702
• Venetoclax

Trial Overview The study is testing the safety of a new drug combo: Q702 with azacitidine and venetoclax in patients whose AML has relapsed or is refractory. It's an early-phase trial to understand how well these drugs work together.

Participant Groups

Group I: Part 2 (Dose Expansion) Experimental Treatment 3 Interventions

Participants receive Q702 orally (PO) once daily (QD) on days 1-7 and 15-21 of each cycle. Azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle and venetoclax PO QD on days 1-21 or days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo collection of blood samples and bone marrow aspiration and/or biopsy throughout the trial.

Group II: Part 1 (Dose Escalation) Experimental Treatment 3 Interventions

Participants receive Q702 orally (PO) once daily (QD) on days 1-7 and 15-21 of each cycle. Azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle and venetoclax PO QD on days 1-21 or days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo collection of blood samples and bone marrow aspiration and/or biopsy throughout the trial.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Qurient Co., Ltd.

Industry Sponsor

Trials

10

Recruited

840+

Findings from Research

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 patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[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 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]

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 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 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]

References

1. 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]

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

TP53 or Not TP53: That Is the Question. [2023]

3. Switzerland 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. [2023]

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

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

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

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022]