We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02530463
Recruitment Status : Active, not recruiting
First Posted : August 21, 2015
Last Update Posted : August 23, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndrome Recurrent Myelodysplastic Syndrome Drug: Azacitidine Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination of Nivolumab and Ipilimumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)
Actual Study Start Date : September 8, 2015
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022


Arm Intervention/treatment
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.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

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.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

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.
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

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.
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

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.
Drug: Azacitidine
Given IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo




Primary Outcome Measures :
  1. 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).

  2. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02530463


Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Guillermo Garcia-Manero M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02530463    
Other Study ID Numbers: 2014-0930
NCI-2015-01494 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0930 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 21, 2015    Key Record Dates
Last Update Posted: August 23, 2022
Last Verified: August 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Myelodysplastic syndrome
MDS
Nivolumab
BMS-936558
Opdivo
Ipilimumab
Yervoy
BMS-734016
MDX010
5-azacitidine
Azacitidine
5-AZA
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Azacytidine
Additional relevant MeSH terms:
Layout table for MeSH terms
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Nivolumab
Ipilimumab
Azacitidine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors