Nivolumab + Ipilimumab + Azacitidine for Myelodysplastic Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Guillermo Garcia-Manero

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

Research Team

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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)

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

Treatment Details

Interventions

• Azacitidine (Chemotherapy)
• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)

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.

Participant Groups

Group I: Cohort VI (azacitidine, nivolumab, ipilimumab) Experimental Treatment 4 Interventions

Patients receive azacitidine IV over 10-40 minutes on days 1-5 and nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 6. Treatment with ipilimumab repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Cycles with nivolumab and azacitidine repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Cohort V (azacitidine, ipilimumab) Experimental Treatment 3 Interventions

Patients receive azacitidine IV over 10-40 minutes on days 1-5 and ipilimumab IV over 30 minutes on day 6. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group III: Cohort IV (azacitidine, nivolumab) Experimental Treatment 3 Interventions

Patients receive azacitidine IV over 10-40 minutes on days 1-5 and nivolumab IV over 30 minutes on days 6 and 20. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group IV: Cohort III (nivolumab, ipilimumab) Experimental Treatment 3 Interventions

Patients receive nivolumab IV over 30 minutes on days 1 and 15 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes every 2 weeks (or every 4 weeks if patients receive azacitidine) in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive ipilimumab, nivolumab, and azacitidine at the discretion of the treating physician.

Group V: Cohort II (ipilimumab) Experimental Treatment 2 Interventions

Patients receive ipilimumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive ipilimumab and azacitidine at the discretion of the treating physician.

Group VI: Cohort I (nivolumab) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive nivolumab and azacitidine at the discretion of the treating physician.

Azacitidine is already approved in Canada, Japan for the following indications:

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School