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

Primary Purpose

Leukemia, Myelodysplastic Syndrome, Recurrent Myelodysplastic Syndrome

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Azacitidine
Ipilimumab
Laboratory Biomarker Analysis
Nivolumab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort I (nivolumab)

Cohort II (ipilimumab)

Cohort III (nivolumab, ipilimumab)

Cohort IV (azacitidine, nivolumab)

Cohort V (azacitidine, ipilimumab)

Cohort VI (azacitidine, nivolumab, ipilimumab)

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR) in MDS Participants with Hypomethylating Agent Failure
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).
Overall Response Rate (ORR) in MDS Participants Who Have Not Received Hypomethylating Agents
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).

Secondary Outcome Measures

Full Information

First Posted
August 19, 2015
Last Updated
September 7, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02530463
Brief Title
Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome
Official Title
Combination of Nivolumab and Ipilimumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 8, 2015 (Actual)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndrome, Recurrent Myelodysplastic Syndrome
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (nivolumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort II (ipilimumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort III (nivolumab, ipilimumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort IV (azacitidine, nivolumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort V (azacitidine, ipilimumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort VI (azacitidine, nivolumab, ipilimumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) in MDS Participants with Hypomethylating Agent Failure
Description
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).
Time Frame
24 weeks
Title
Overall Response Rate (ORR) in MDS Participants Who Have Not Received Hypomethylating Agents
Description
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).
Time Frame
30 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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