Azacitidine + Nivolumab/Midostaurin vs. Decitabine/Cytarabine for Acute Myeloid Leukemia

Recruiting at 571 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Midostaurin, Anti-PD-1, Anti-PD-L1

Disqualifiers: CNS AML, Active infection, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II/III trial studies how well azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone work in treating older patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as azacitidine, decitabine, and 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. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone may kill more cancer cells.

Research Team

Laura C Michaelis

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for older adults with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Participants must not need concurrent cancer therapy (except hormonal), have acceptable liver function, be able to swallow pills, and consent to specimen banking. Women of childbearing age and sexually active men must use effective contraception. Those with central nervous system leukemia, prior specific treatments like midostaurin or DNA-methyltransferase inhibitors, or who are pregnant/nursing are excluded.

Inclusion Criteria

I can swallow pills without needing to crush or chew them.

I have had cancer before, but it doesn't need current treatment.

I have been diagnosed with AML or MDS-EB-2 and have not received treatment.

Treatment Details

Interventions

• Azacitidine
• Cytarabine
• Decitabine
• Midostaurin
• Nivolumab

Trial Overview The study compares the effectiveness of azacitidine alone versus in combination with nivolumab (an immunotherapy) or midostaurin (a growth blocker), against decitabine and cytarabine alone in treating certain blood cancers. It aims to determine which treatment stops cancer cells from growing by either killing them directly or boosting the immune response against them.

Participant Groups

Group I: Arm D (decitabine, cytarabine) Experimental Treatment 3 Interventions

INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (azacitidine, midostaurin) Experimental Treatment 3 Interventions

Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: Arm B (azacitidine, nivolumab) Experimental Treatment 3 Interventions

Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (azacitidine) Active Control 2 Interventions

Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+