76 Participants Needed

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

Recruiting at 578 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with newly diagnosed acute myeloid leukemia (AML) or a high-risk type of myelodysplastic syndrome (MDS). It compares the effectiveness of various drug combinations, including azacitidine (a chemotherapy drug) with or without nivolumab (an immunotherapy drug) or midostaurin, and decitabine with cytarabine, to determine which best stops cancer growth. The study seeks participants who have not yet received treatment for AML or high-risk MDS and who cannot or choose not to undergo intense chemotherapy. Participants will help researchers determine if these treatments can better control the disease and improve outcomes. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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

Research has shown that the treatments in this trial have varying safety levels based on past studies. Studies indicate that the combination of azacitidine and nivolumab is generally safe for patients with acute myeloid leukemia (AML), with positive response rates and survival outcomes. Research on azacitidine with midostaurin suggests it is a safe and effective option for patients with AML and high-risk myelodysplastic syndrome (MDS).

The combination of decitabine and cytarabine has been shown to be well-tolerated in older patients with high-risk AML, improving their outlook and offering promising results. While these treatments are usually safe, each may have its own side effects. Patients should discuss potential risks and benefits with their healthcare providers before joining a clinical trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute myeloid leukemia (AML) because they explore new combinations and mechanisms that could enhance patient outcomes. Unlike many standard AML treatments that primarily rely on chemotherapy agents like cytarabine and anthracyclines, the investigational combinations include azacitidine with either nivolumab or midostaurin, offering unique approaches. Nivolumab is an immunotherapy that targets the PD-1 pathway, potentially boosting the immune system's ability to fight cancer cells. Midostaurin is a targeted therapy known for inhibiting certain enzymes that promote cancer cell growth. These therapies could potentially offer improved effectiveness and safety profiles compared to traditional options.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various drug combinations for acute myeloid leukemia (AML). Research has shown that combining azacitidine with nivolumab, which participants in Arm B may receive, can help patients with AML live longer and achieve complete remission, meaning the cancer becomes undetectable. In Arm C, azacitidine is combined with midostaurin, which studies indicate significantly improves survival, especially for those with specific genetic mutations. Meanwhile, Arm D involves the combination of decitabine and cytarabine, which has shown promise for older AML patients, improving their outlook and achieving high response rates. Each of these drug combinations works differently to stop cancer cells from growing and spreading.13567

Who Is on the Research Team?

LC

Laura C Michaelis

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.
See 34 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, up to 2 cycles for induction

Maintenance

Patients deemed stable receive maintenance therapy with decitabine. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years
Every 3 months for the 1st year, every 6 months for the 2nd and 3rd years, then annually

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm D (decitabine, cytarabine)Experimental Treatment3 Interventions
Group II: Arm C (azacitidine, midostaurin)Experimental Treatment3 Interventions
Group III: Arm B (azacitidine, nivolumab)Experimental Treatment3 Interventions
Group IV: Arm A (azacitidine)Active Control2 Interventions

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Vidaza for:
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Approved in United States as Vidaza for:
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Approved in Canada as Vidaza for:
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Approved in Japan as Vidaza for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

What to use to treat AML: the role of emerging therapiesEarly trials have combined APR-246 with azacitidine in MDS and AML. In a phase 1/2 trial, the ORR was 64% with a 36% CR rate in TP53-mutated AML patients.
Rydapt (midostaurin) vs Onureg (azacitidine)Patients who received Rydapt in addition to chemotherapy experienced a median overall survival of 74.7 months, compared to 25.6 months for those who received ...
Oral Azacitidine Maintenance Therapy for Acute Myeloid ...CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in ...
FLT3 mutated acute myeloid leukemia - blood cancer journalResults of venetoclax and azacitidine combination in chemotherapy ineligible untreated patients with acute myeloid leukemia with FLT3 mutations.
Targeting FLT3 and KIT Mutations in AML with MidostaurinThe clinical efficacy of midostaurin has been evaluated in many clinical trials. Treatment with midostaurin demonstrated a significant survival benefit in ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/25530214/
Phase I/II trial of the combination of midostaurin (PKC412) and ...The combination of midostaurin and AZA is an effective and safe regimen in patients with AML and high-risk MDS. Patients with FLT3 mutations but not previously ...
Management of toxicities associated with targeted therapies ...This review article discusses the unique toxicities associated with currently approved targeted therapies for AML, including both mutation-specific and ...
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