Clinical Trials /

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

NCT02530463

Description:

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab With 5-azacitidine in Patients With Myelodysplastic Syndromes (MDS)
  • Official Title: Combination of Nivolumab and Ipilimumab With 5-azacitidine in Patients With Myelodysplastic Syndromes (MDS)

Clinical Trial IDs

  • ORG STUDY ID: 2014-0930
  • SECONDARY ID: NCI-2015-01494
  • NCT ID: NCT02530463

Conditions

  • Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
NivolumabBMS-936558, OpdivoCohort 1 - Nivolumab
IpilimumabYervoy, BMS-734016, MDX010Cohort 2 - Ipilimumab
5-azacitidineAzacitidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, AzacytidineCohort 4 - 5-azacitidine + Nivolumab

Purpose

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.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to 1 of 6
      study cohorts, based on when you join this study and on what treatments you have already
      received. Participants who have already received treatments called hypomethylating agents
      will be in Cohorts 1-3. Participants who have not received treatment will be in Cohorts 4-6:

        -  If you are in Cohort 1, you will receive nivolumab.

        -  If you are in Cohort 2, you will receive ipilimumab.

        -  If you are in Cohort 3, you will receive nivolumab and ipilimumab.

        -  If you are in Cohort 4, you will receive azacitidine and nivolumab.

        -  If you are in Cohort 5, you will receive azacitidine and ipilimumab.

        -  If you are in Cohort 6, you will receive azacitidine, nivolumab, and ipilimumab.

      Study Drug Administration:

      Study cycles for Cohorts 1-3 will be 3-4 weeks long. Study cycles for Cohorts 4-6 will be 4
      weeks long.

      If you receive nivolumab, you will receive it by vein over about 1 hour on Days 1 and 15. If
      you receive ipilimumab, you will receive it by vein over about 90 minutes on Day 1 for 6
      cycles. If you receive azacitidine, you will receive it by vein over about 10-40 minutes for
      5 days every 4 weeks, then receive the other drug(s) as described above on Days 6 and/or 20
      of each cycle.

      If you are in Cohorts 1-3 and the doctor thinks it is in your best interest, you may begin
      to receive azacitidine after Cycle 6.

      Study Visits:

      One (1) time each week during Cycle 1, and then one time during every cycle after that:

        -  You will have a physical exam.

        -  Blood (about 2-3 teaspoons) will be drawn for routine tests.

      These tests may be done more often if your doctor thinks it is needed.

      If the doctor thinks it is needed, on Day 21 or 28 of Cycles 1 (depending on to which cohort
      you are assigned) and then every 3 months, you will have a bone marrow aspiration to check
      the status of the disease and for cytogenetic testing.

      If you can become pregnant, you will have a urine or blood (about 1 teaspoon) pregnancy test
      every 6 weeks.

      Length of Treatment:

      You may continue taking the study drug(s) for as long as the doctor thinks it is in your
      best interest. You will no longer be able to take the study drug(s) if the disease gets
      worse, if intolerable side effects occur, or if you are unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      Follow-up visits:

      If you can become pregnant, you will have a urine or blood (about 1 teaspoon) pregnancy test
      30 and 70 days after you have stopped taking the study drugs.

      There are additional laboratory research studies that you may be eligible for that may help
      researchers learn more about the disease. You will be given separate consent forms for these
      studies that explain their goals and risks.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 - NivolumabExperimentalHypomethylating 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.
  • Nivolumab
Cohort 2 - IpilimumabExperimentalHypomethylating 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.
  • Ipilimumab
Cohort 3 - Nivolumab + IpilimumabExperimentalHypomethylating failure MDS cohort: Nivolumab and Ipilimumab Nivolumab 3 mg/kg by vein every 2 weeks for 6 cycles. 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.
  • Nivolumab
  • Ipilimumab
Cohort 4 - 5-azacitidine + NivolumabExperimentalPreviously 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 5 weeks.
  • Nivolumab
  • 5-azacitidine
Cohort 5 - 5-azacitidine + IpilimumabExperimentalPreviously 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 3 weeks. A cycle considered 5 weeks.
  • Ipilimumab
  • 5-azacitidine
Cohort 6 - 5-azacitidine + Nivolumab + IpilimumabExperimentalPreviously 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 by Nivolumab 3 mg/kg by vein every 2 weeks and Ipilimumab 3 mg/kg by vein every 3 weeks. A cycle considered 5 weeks.
  • Nivolumab
  • Ipilimumab
  • 5-azacitidine

Eligibility 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 </=2.5 x ULN; serum bilirubin </=2.5 x ULN; AST
             and ALT </=2.5 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 that has not been definitively treated
             or 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. Treatment for MDS with any other drug not being an HMA. Prior treatment with growth
             factors, lenalidomide, and any HMA is allowed.

         13. More than 4 months since last cycle of HMA (in previously treated patients).

         14. Prior treatment with allogeneic stem cell transplantation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) in MDS Participants with Hypomethylating Agent Failure
Time Frame:24 weeks
Safety Issue:
Description:Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial 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

Last Updated

March 28, 2017