Combination Chemotherapy for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Tapan Kadia, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Venetoclax

Disqualifiers: Pregnancy, Uncontrolled illness, APL, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that has previously not been treated. Drugs used in chemotherapy, such as venetoclax, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, cladribine, low dose cytarabine induction followed by cladribine, low dose cytarabine, and azacitidine consolidation may work better in treating patients with acute myeloid leukemia.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, prior therapy with certain drugs like hydroxyurea and cytarabine is allowed, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this drug combination for treating acute myeloid leukemia?

Research shows that combining venetoclax with azacitidine improves remission rates and survival in older patients with acute myeloid leukemia compared to azacitidine alone. Additionally, the combination of venetoclax and azacitidine has become a first-line therapy for elderly patients, achieving a high complete remission rate. ^{1 2 3 4 5}

Is the combination of venetoclax and azacitidine safe for humans?

The combination of venetoclax and azacitidine has been found to have acceptable safety in patients with acute myeloid leukemia, including those who are older or have relapsed. It is generally well-tolerated, but as with any treatment, there may be side effects, and long-term safety data is still being observed. ^{3 5 6 7 8}

What makes the combination chemotherapy with Azacitidine, Cladribine, Cytarabine, and Venetoclax unique for treating acute myeloid leukemia?

This treatment is unique because it combines multiple drugs, including venetoclax, which is known to improve remission rates and survival in older or unfit patients with acute myeloid leukemia when combined with azacitidine. The addition of cladribine and cytarabine may further enhance outcomes, offering a potentially more effective option for patients who are not candidates for standard chemotherapy. ^{2 4 6 7 8}

Eligibility Criteria

This trial is for adults under 50 with untreated acute myeloid leukemia (AML), who can't have standard therapy. They must have normal liver and kidney function, be physically stable enough to participate, not pregnant or breastfeeding, willing to use contraception, and able to consent.

Inclusion Criteria

I understand the study's requirements and have signed the consent form.

I have AML and may have had only specific minor treatments.

I am 50 years or older, or under 50 but considered unsuitable for standard treatment.

Exclusion Criteria

I am of childbearing age and do not use birth control.

Participants with documented hypersensitivity to any of the components of the chemotherapy program

I have been diagnosed with acute promyelocytic leukemia.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive cladribine, cytarabine, and venetoclax for 28 days. A second induction cycle may be given if CR or CRi is not achieved.

4 weeks

Daily visits for drug administration

Consolidation/Maintenance

Patients receive cladribine, cytarabine, venetoclax, and azacitidine in cycles, repeating every 28 days for up to 18 cycles.

Up to 18 months

Regular visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 6-12 months for 5 years

Treatment Details

Interventions

• Azacitidine (DNA Methyltransferase Inhibitor)
• Cladribine (Purine analogues)
• Cytarabine (Pyrimidine analogues)
• Venetoclax (B-cell lymphoma 2 (BCL-2) inhibitor)

Trial Overview The study tests a combination of chemotherapy drugs: Venetoclax, Cladribine, low dose Cytarabine, and Azacitidine in two phases—induction followed by consolidation—to see if they're more effective together in treating AML.

Participant Groups

Group I: Treatment (cladribine, cytarabine, venetoclax, azacitidine) Experimental Treatment 4 Interventions

See Detailed Description.

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:

M D Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

References

1. China 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]. [2023] To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML).

2. 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.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. [2023] To retrospectively analyze the efficacy and safety of venetoclax combined with azacitidine (VEN + AZA) in the treatment of elderly patients with acute myeloid leukemia. The clinical data for 57 AML patients treated with the VEN + AZA regimen from December 2019 to November 2022 in the Department of Hematology, General Hospital of Tianjin Medical University, were collected. Of the 57 patients included in this study, the mean age of onset was 69.89 (±8.88) years. The median follow-up time was 8.57 months, and the median OS time was 11.50 months. The ORR, CR rate, and MRD (

4. 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

5. England 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. [2023] The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

6. 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.

7. 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.

8. China pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022] Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.