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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of a new drug combination for treating acute myeloid leukemia (AML) that has relapsed or is resistant to treatment. The drugs being tested are Q702 (an experimental treatment), azacitidine, and venetoclax. Participants will take these drugs in cycles, with some doses administered orally and others through an IV. Suitable candidates have AML that has relapsed or is unresponsive to standard treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that the combination of azacitidine and venetoclax is generally well-tolerated by patients with acute myeloid leukemia (AML). These drugs have helped some patients achieve remission and live longer. However, the addition of the drug Q702 to this combination remains under study, so complete safety information is not yet available.

As this trial is in its early stages, the primary goal is to assess safety and patient tolerance. Researchers are still gathering data on side effects and will closely monitor participants to address any issues promptly.

In summary, while azacitidine and venetoclax have shown promise, the effects of adding Q702 are still under investigation. Participants should discuss any concerns with their healthcare provider to fully understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for acute myeloid leukemia (AML) because it introduces Q702, a novel agent that potentially enhances the efficacy of existing therapies. Unlike the standard treatments, which typically include azacitidine and venetoclax alone, this approach integrates Q702, which targets specific pathways that could improve cancer cell death. The combination of Q702 with azacitidine and venetoclax might offer a more potent strategy against AML by disrupting cancer growth more effectively. This innovative combo could lead to better outcomes and offers hope for patients who haven't responded well to current treatments.

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

Research has shown that combining venetoclax with azacitidine can extend the lives of some adults with acute myeloid leukemia (AML) more effectively than azacitidine alone. This combination has shown promise in increasing overall survival. In this trial, researchers are testing a new drug, Q702, alongside venetoclax and azacitidine to determine if it can further enhance outcomes. Early studies in this trial focus on ensuring the safety and manageability of this new combination for patients. Overall, this treatment holds potential for aiding those with AML that has recurred or is resistant to other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Abhishek Maiti, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

My liver is working well.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06445907

Phase I Study of Q702 With Azacitidine and Venetoclax for ... To learn about the safety and tolerability of the drug combination of Q702, azacitidine, and venetoclax when given to participants with relapsed/refractory AML.

2. venclextahcp.com venclextahcp.com/aml/efficacy/ven-aza/survival-results.html

VEN+AZA: Overall survival (OS) data from the VIALE-A trial See median overall survival data for VENCLEXTA® combined with azacitidine compared with azacitidine. See full safety and Prescribing Info for more details.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38899566/

Outcomes of acute myeloid leukemia patients who ... This study suggests that patients who discontinued treatment in remission have favorable outcomes supporting the rationale for prospective controlled trials.

4. venclexta.com venclexta.com/aml/why-venclexta/venclexta-azacitidine

How Effective is VENCLEXTA® + azacitidine Against AML? In a clinical study, VENCLEXTA + azacitidine was found to help some adults with AML live longer than those treated with azacitidine alone.

5. ctsearchsupport.org ctsearchsupport.org/clinical-trials/phase-i-study-of-q702-with-azacitidine-and-venetoclax-for-relapsed-or-refractory-acute-myeloid-leukemia

Trial Summary | NMDP℠ CTSS If the combination of azacitidine , Q702 and venetoclax is safe and works well to treat AML that has relapsed or is refractory. You may be able ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5994/527611/Phase-1-Study-of-AXL-MER-CSF1R-Inhibitor-Q702-with

Phase 1 Study of AXL/MER/CSF1R Inhibitor Q702 with ... Primary objective is to study the safety and tolerability of Q702 in combination with venetoclax and azacitidine. Secondary objectives are to ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06445907/phase-i-study-of-q702-with-azacitidine-and-venetoclax-for-relapsed-or-refractory-acute-myeloid-leukemia

Phase I Study of Q702 With Azacitidine and Venetoclax for ... To learn about the safety and tolerability of the drug combination of Q702, azacitidine, and venetoclax when given to participants with relapsed ...

8. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-10-2024-7efe9

Q702 + Azacitidine + Venetoclax for 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 ...