Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome

March 3, 2026 updated by: M.D. Anderson Cancer Center

Combination of Nivolumab and Ipilimumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of nivolumab and ipilimumab, as single agents or in combination and with 5-azacitidine (azacitidine), in patients with myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

I. To explore the clinical activity of nivolumab and ipilimumab, as single agents or in combination and with 5-azacitidine, in patients with MDS.

II. To explore the biological activity of these compounds in patients with MDS.

OUTLINE: Patients are assigned to 1 of 6 cohorts. Patients with hypomethylating failure MDS are assigned to cohorts I, II, or III. Patients with previously untreated MDS are assigned to cohorts IV, V, or VI.

COHORT I (COHORT COMPLETED AS OF 10/7/19): Patients receive nivolumab intravenously (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.

COHORT II (COHORT COMPLETED AS OF 10/7/19): 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.

COHORT III: 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.

COHORT IV (COHORT COMPLETED AS OF 10/7/19): 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.

COHORT V: 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.

COHORT VI (COHORT ON-HOLD AS OF 10/7/19): 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
99

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with MDS (up to 20% blasts) of any risk as defined as:

    • Previously untreated
    • Previously treated with hypomethylating agent (HMA) agent; patients need to have relapsed or progressed after any number of cycles of HMA therapy; patients that do not respond to HMA therapy will also be allowed in the study; relapse or progression will be measured by International Working Group (IWG) 2006 criteria; no response will be lack of clinical benefit after at least 6 cycles of HMA therapy
  • Creatinine =< 2.0 x upper limit of normal (ULN)
  • Serum bilirubin =< 2.0 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.0 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drugs; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
  • Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and a period of 31 weeks after the last dose of investigational drug
  • Patients or their legally authorized representative must provide written informed consent

Exclusion Criteria:

  • Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy
  • Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs
  • 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
  • Patients unwilling or unable to comply with the protocol
  • History of pneumonitis
  • Patients who are on high dose steroid (equivalent of prednisone more than 10 mg a day) or immune suppression medications
  • Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
  • Patients with a history of inflammatory bowel disease such as Crohn's disease and ulcerative colitis
  • Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months); patients with history of human immunodeficiency virus (HIV) disease are also excluded from the study
  • Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents
  • Females who are pregnant or lactating
  • Prior treatment with allogeneic stem cell transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort I (nivolumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Experimental: Cohort II (ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Experimental: Cohort III (nivolumab, ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Experimental: Cohort IV (azacitidine, nivolumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Experimental: Cohort V (azacitidine, ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Experimental: Cohort VI (azacitidine, nivolumab, ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) in MDS Participants with Hypomethylating Agent Failure
Time Frame: 24 weeks
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).
24 weeks
Overall Response Rate (ORR) in MDS Participants Who Have Not Received Hypomethylating Agents
Time Frame: 30 weeks
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).
30 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guillermo Garcia-Manero, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 8, 2015

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 19, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 21, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-0930 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2015-01494 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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