Ziftomenib + Venetoclax + Azacitidine for Childhood Acute Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by David McCall, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Antileukemic, Antivirals, others

Disqualifiers: Uncontrolled infection, Active malignancy, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

To find the highest safe dose of ziftomenib that can be combined with venetoclax and azacitidine in pediatric participants with acute leukemia that has certain types of genetic mutations (changes).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it does not allow other chemotherapeutic or anti-leukemic agents during the study, except for certain exceptions like intrathecal chemotherapy for CNS leukemia and hydroxyurea for rapidly proliferative disease. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination Ziftomenib, Venetoclax, and Azacitidine for treating childhood acute leukemia?

Research shows that the combination of Venetoclax and Azacitidine improves remission rates and survival in older patients with acute myeloid leukemia, suggesting potential effectiveness in similar conditions. ^{1 2 3 4 5}

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

This drug combination is unique because it includes Ziftomenib, which is not commonly used in standard treatments for acute leukemia. While Venetoclax and Azacitidine are already used together for certain types of leukemia, adding Ziftomenib may offer a new approach, potentially targeting different pathways in the cancer cells. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for children with acute leukemia that has come back or hasn't responded to treatment. They must have specific genetic mutations in their cancer cells. The exact criteria for who can join are not provided, but typically include age range and health status.

Inclusion Criteria

I agree to use birth control during and after the study for the required time.

I am currently receiving treatment for brain disease prevention or control.

It has been over 14 days since my last cancer treatment, or 5 half-lives of the medication.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have active hepatitis B or C, nor uncontrolled HIV/AIDS.

I am not using other cancer drugs during this study, except for allowed exceptions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive escalating doses of ziftomenib to determine the maximum tolerated dose

Varies based on dose escalation protocol

Dose-expansion

Participants receive the recommended Phase II dose of ziftomenib in combination with venetoclax and azacitidine

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azacitidine (Anti-metabolites)
• Venetoclax (BCL-2 Inhibitor)
• Ziftomenib (Other)

Trial Overview The study aims to find the safest high dose of a drug called Ziftomenib when used with Venetoclax and Azacitidine in kids with certain types of acute leukemia. It's an early-phase trial focused on dosage safety.

Participant Groups

Group I: Dose-escalation + Dose-expansion of Ziftomenib Experimental Treatment 3 Interventions

The first group of 3 participants will receive the starting dose of ziftomenib. If no intolerable side effects are seen, the rest of the study participants will receive a higher dose of ziftomenib. If intolerable side effects were seen at the starting dose, the next group of 3 participants will receive a lower total dose given for a shorter time period. If needed for safety, an even lower total dose schedule can be assigned to the next group of participants.

Azacitidine is already approved in European Union, United States, Canada, Japan, Australia 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

🇦🇺 Approved in Australia as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

Kura Oncology, Inc. Industry Sponsor

References

1. 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] Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN.

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

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023] The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

3. England pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021] Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities.

4. 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] The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

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

TP53 or Not TP53: That Is the Question. [2023] Azacitidine and venetoclax are a standard first-line regimen for patients with newly diagnosed unfit acute myeloid leukemia (AML). In a pooled subset analysis, TP53-mutated AML with poor-risk cytogenetics does not appear to benefit from the addition of venetoclax to azacitidine. This has clinical implications as these patients should be preferentially treated with alternative regimens. See related article by Pollyea et al., p. 5272.

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

Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. [2022] Venetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is