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Nivolumab and Ipilimumab With 5-azacitidine in Patients With Myelodysplastic Syndromes (MDS)

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ClinicalTrials.gov Identifier: NCT02530463
Recruitment Status : Recruiting
First Posted : August 21, 2015
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if nivolumab and/or ipilimumab, with or without azacitidine, are safe to give to patients with MDS. Researchers also want to learn if the study drug combinations can help to control the disease.

This is an investigational study. Nivolumab and ipilimumab are not FDA approved or commercially available for the treatment of MDS. Nivolumab and ipilimumab are each approved for the treatment of melanoma. Their use in MDS is investigational. Azacitidine is approved by the FDA for the treatment of MDS. The use of these drugs in combination is investigational.

Up to 120 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndrome Drug: Nivolumab Drug: Ipilimumab Drug: 5-azacitidine Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 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 2021
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Experimental: Cohort 1 - Nivolumab

Hypomethylating failure MDS cohort: Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. One cycle defined as 4 weeks.

After 6 cycles (or earlier if evidence of progression), the use of azacitidine (AZA) allowed to test the concept of re-sensitization.

Drug: Nivolumab

Cohort 1: Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. One cycle defined as 4 weeks.3 mg/kg by vein every 2 weeks.

Cohort 3: Nivolumab 3 mg/kg by vein on days 1 and 15 (i.e. 2 planned doses of Nivolumab)

Cohort 4: Nivolumab 3 mg/kg by vein on day 6 after 5 days of Azacitidine.

Cohort 6: Nivolumab 3 mg/kg by vein on day 6 and day 20 after 5 days of Azacitidine.

Other Names:
  • BMS-936558
  • Opdivo

Experimental: Cohort 2 - Ipilimumab

Hypomethylating failure MDS cohort: Ipilimumab 3 mg/kg by vein every 3 weeks. One cycle defined as 4 weeks.

After 6 cycles (or earlier if evidence of progression), the use of AZA allowed to test the concept of re-sensitization.

Drug: Ipilimumab

Cohort 2, 3 , and 5: Ipilimumab 3 mg/kg by vein every 3 weeks.

Cohort 5: Ipilimumab 3 mg/kg by vein every 4 weeks.

Cohort 6: Ipilimumab 3 mg/kg by vein on day 6 following 5 days of Azacitidine.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Experimental: Cohort 3 - Nivolumab + Ipilimumab

Hypomethylating failure MDS cohort: Nivolumab and Ipilimumab

Nivolumab 3 mg/kg by vein on days 1 and 15 (i.e. 2 planned doses of Nivolumab) and Ipilimumab 3 mg/kg by vein on day 1. One cycle defined as 4 weeks.

After 6 cycles (or earlier if evidence of progression), the use of AZA allowed to test the concept of re-sensitization.

Drug: Nivolumab

Cohort 1: Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. One cycle defined as 4 weeks.3 mg/kg by vein every 2 weeks.

Cohort 3: Nivolumab 3 mg/kg by vein on days 1 and 15 (i.e. 2 planned doses of Nivolumab)

Cohort 4: Nivolumab 3 mg/kg by vein on day 6 after 5 days of Azacitidine.

Cohort 6: Nivolumab 3 mg/kg by vein on day 6 and day 20 after 5 days of Azacitidine.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab

Cohort 2, 3 , and 5: Ipilimumab 3 mg/kg by vein every 3 weeks.

Cohort 5: Ipilimumab 3 mg/kg by vein every 4 weeks.

Cohort 6: Ipilimumab 3 mg/kg by vein on day 6 following 5 days of Azacitidine.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Experimental: Cohort 4 - 5-azacitidine + Nivolumab

Previously untreated MDS cohort: Azacitidine and Nivolumab

Azacitidine 75 mg/m2 by vein daily for 5 days every 4 weeks followed on day 6 by Nivolumab 3 mg/kg by vein every 2 weeks. A cycle considered 4 weeks.

Drug: Nivolumab

Cohort 1: Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. One cycle defined as 4 weeks.3 mg/kg by vein every 2 weeks.

Cohort 3: Nivolumab 3 mg/kg by vein on days 1 and 15 (i.e. 2 planned doses of Nivolumab)

Cohort 4: Nivolumab 3 mg/kg by vein on day 6 after 5 days of Azacitidine.

Cohort 6: Nivolumab 3 mg/kg by vein on day 6 and day 20 after 5 days of Azacitidine.

Other Names:
  • BMS-936558
  • Opdivo

Drug: 5-azacitidine
Cohort 4,5, and 6: 75 mg/m2 by vein for 5 days every 4 weeks
Other Names:
  • Azacitidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Azacytidine

Experimental: Cohort 5 - 5-azacitidine + Ipilimumab

Previously untreated MDS cohort: 5-azacitidine and Ipilimumab

Azacitidine 75 mg/m2 by vein daily for 5 days every 4 weeks followed on day 6 by Ipilimumab 3 mg/kg by vein every 4 weeks. A cycle considered 4 weeks.

Drug: Ipilimumab

Cohort 2, 3 , and 5: Ipilimumab 3 mg/kg by vein every 3 weeks.

Cohort 5: Ipilimumab 3 mg/kg by vein every 4 weeks.

Cohort 6: Ipilimumab 3 mg/kg by vein on day 6 following 5 days of Azacitidine.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Drug: 5-azacitidine
Cohort 4,5, and 6: 75 mg/m2 by vein for 5 days every 4 weeks
Other Names:
  • Azacitidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Azacytidine

Experimental: Cohort 6 - 5-azacitidine + Nivolumab + Ipilimumab

Previously untreated MDS cohort: Azacitidine with Nivolumab and Ipilimumab

Azacitidine 75 mg/m2 by vein daily for 5 days every 4 weeks followed on day 6 and day 20 by Nivolumab 3 mg/kg by vein and Ipilimumab 3 mg/kg by vein on day 6. A cycle considered 4 weeks.

Drug: Nivolumab

Cohort 1: Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. One cycle defined as 4 weeks.3 mg/kg by vein every 2 weeks.

Cohort 3: Nivolumab 3 mg/kg by vein on days 1 and 15 (i.e. 2 planned doses of Nivolumab)

Cohort 4: Nivolumab 3 mg/kg by vein on day 6 after 5 days of Azacitidine.

Cohort 6: Nivolumab 3 mg/kg by vein on day 6 and day 20 after 5 days of Azacitidine.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab

Cohort 2, 3 , and 5: Ipilimumab 3 mg/kg by vein every 3 weeks.

Cohort 5: Ipilimumab 3 mg/kg by vein every 4 weeks.

Cohort 6: Ipilimumab 3 mg/kg by vein on day 6 following 5 days of Azacitidine.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Drug: 5-azacitidine
Cohort 4,5, and 6: 75 mg/m2 by vein for 5 days every 4 weeks
Other Names:
  • Azacitidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Azacytidine




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.


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

Inclusion Criteria:

  1. Patients with MDS (up to 20% blasts) of any risk as defined as: a. Previously untreated; b. Previously treated with 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 IWG 2006 criteria. No response will be lack of clinical benefit after at least 6 cycles of HMA therapy.
  2. Age 18 years or older.
  3. Adequate organ function: creatinine </=2.0 x ULN; serum bilirubin </=2.0 x ULN; AST and ALT </=2.0 x ULN.
  4. ECOG performance status </=2
  5. Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (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.
  6. 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.
  7. Patients or their legally authorized representative must provide written informed consent.

Exclusion Criteria:

  1. History of another primary invasive malignancy unless definitively treated or unless in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
  2. Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs.
  3. Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure 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.
  4. Patients unwilling or unable to comply with the protocol.
  5. History of pneumonitis.
  6. Patients who are on high dose steroid (equivalent of prednisone more than 10 mg a day) or immune suppression medications.
  7. Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]).
  8. Patients with a history of Inflammatory Bowel Disease such as Crohn's disease and ulcerative colitis.
  9. 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 HIV disease are also excluded from the study.
  10. Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents.
  11. Females who are pregnant or lactating.
  12. For hypomethylating failure cohorts, treatment for MDS with any other drug not being an HMA with the following exceptions: Prior treatment with growth factors and/or lenalidomide is allowed for any cohort.
  13. For hypomethylating failure cohorts only, more than 4 months since last cycle of HMA.
  14. 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


Contacts
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Contact: Guillermo Garcia-Manero, MD 713-745-3428 ggarciam@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
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Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02530463     History of Changes
Other Study ID Numbers: 2014-0930
NCI-2015-01494 ( Other Identifier: NCI CTRP )
First Posted: August 21, 2015    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019

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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:
Myelodysplastic syndrome
MDS
Nivolumab
Opdivo
Leukemia
BMS-936558
Ipilimumab
Yervoy
BMS-734016
MDX010
5-azacitidine
Azacitidine
5-AZA
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Azacytidine

Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Preleukemia
Nivolumab
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Ipilimumab
Azacitidine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors