99 Participants Needed

Nivolumab + Ipilimumab + Azacitidine for Myelodysplastic Syndrome

GG
Overseen ByGuillermo Garcia-Manero
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 phase II trial studies the side effects of nivolumab and/or ipilimumab with or without azacitidine and to see how well they work in treating patients with myelodysplastic syndrome. Monoclonal antibodies, such as nivolumab and ipilimumab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as azacitidine, 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. Giving nivolumab and/or ipilimumab with or without azacitidine may work better in treating myelodysplastic syndrome.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high-dose steroids or immune suppression medications, you may not be eligible to participate.

Is the combination of Nivolumab, Ipilimumab, and Azacitidine safe for humans?

Azacitidine has been studied for safety in patients with myelodysplastic syndrome and other blood disorders, showing some common side effects like pneumonia, joint pain, and constipation. In combination with other drugs, it has been generally safe with manageable side effects, but specific safety data for the combination with Nivolumab and Ipilimumab is not provided in the available research.12345

How is the drug combination of Nivolumab, Ipilimumab, and Azacitidine unique for treating Myelodysplastic Syndrome?

This drug combination is unique because it combines immune checkpoint inhibitors (Nivolumab and Ipilimumab) with Azacitidine, a drug that affects DNA methylation, potentially offering a novel approach by enhancing the immune system's ability to fight cancer cells in Myelodysplastic Syndrome, a condition with limited standard treatment options.678910

What data supports the effectiveness of the drug azacitidine for myelodysplastic syndrome?

Azacitidine has been shown to significantly improve survival in patients with higher-risk myelodysplastic syndromes compared to conventional care, with studies reporting longer median overall survival times and reduced transfusion needs.211121314

Who Is on the Research Team?

Guillermo Garcia-Manero | MD Anderson ...

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Myelodysplastic Syndrome (MDS) who have previously been treated with hypomethylating agents but didn't respond well or the disease came back. They should not have had a stem cell transplant, any other cancer treatments, or major surgery within 2 weeks before starting the study. Participants need to be relatively healthy otherwise and can't be pregnant, breastfeeding, or have certain autoimmune diseases.

Inclusion Criteria

I will use effective birth control during and for 31 weeks after the study.
Patients or their legally authorized representative must provide written informed consent
Creatinine =< 2.0 x upper limit of normal (ULN)
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Exclusion Criteria

I am not pregnant or breastfeeding.
I haven't had major surgery or cancer treatment in the last 2 weeks.
Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab, ipilimumab, and/or azacitidine based on cohort assignment. Treatment cycles repeat every 3-4 weeks depending on the cohort.

24-30 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Azacitidine
  • Ipilimumab
  • Nivolumab
Trial Overview The trial is testing how effective and safe it is to use Nivolumab and/or Ipilimumab with or without Azacitidine in treating MDS. These drugs include monoclonal antibodies that may block cancer growth by targeting specific cells and chemotherapy that stops cancer cells from growing.
How Is the Trial Designed?
6Treatment groups
Experimental Treatment
Group I: Cohort VI (azacitidine, nivolumab, ipilimumab)Experimental Treatment4 Interventions
Group II: Cohort V (azacitidine, ipilimumab)Experimental Treatment3 Interventions
Group III: Cohort IV (azacitidine, nivolumab)Experimental Treatment3 Interventions
Group IV: Cohort III (nivolumab, ipilimumab)Experimental Treatment3 Interventions
Group V: Cohort II (ipilimumab)Experimental Treatment2 Interventions
Group VI: Cohort I (nivolumab)Experimental Treatment2 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.
The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.
Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study).Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]
Azacitidine significantly improves overall survival in patients with myelodysplastic syndromes and related disorders, with a median survival of 24.5 months compared to 15 months for conventional care, based on a trial of 358 patients.
While azacitidine offers a viable treatment option when stem cell transplantation is not possible, it carries risks of severe toxicity and other side effects, highlighting the need for careful patient management.
Azacitidine. Poor-prognosis myelodysplasia: promising, but more data needed.[2013]
Azacitidine has been shown to significantly prolong the time to progression to acute myeloid leukemia or death in myelodysplastic syndromes (MDS) patients, with a median time of 21 months compared to 13 months for supportive care in a study of 191 patients.
In a larger trial with 358 patients, azacitidine also significantly improved overall survival, extending it to 24.5 months compared to 15.0 months with conventional care, establishing it as a key first-line treatment for higher-risk MDS patients.
Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes.Fenaux, P., Ades, L.[2022]

Citations

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). [2019]
Azacitidine. Poor-prognosis myelodysplasia: promising, but more data needed. [2013]
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. [2022]
Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes. [2022]
Minimizing risk of hypomethylating agent failure in patients with higher-risk MDS and practical management recommendations. [2022]
Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. [2015]
Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. [2021]
Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. [2022]
Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome. [2021]
Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. [2023]
Nivolumab-induced plaque morphea in a malign melanoma patient. [2021]
Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod. [2020]
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