Clinical Trials /

Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

NCT02599649

Description:

The goal of this clinical research study is to learn if lirilumab and Opdivo (nivolumab), alone or in combination with Vidaza (azacitidine), can help to control MDS. The safety of these drug combinations will also be studied. This is an investigational study. Lirilumab is not FDA approved or commercially available. It is currently being used for research purposes. Nivolumab is FDA approved and commercially available for the treatment of melanoma and non small cell lung cancer (NSCLC). Azacitidine is FDA approved and commercially available for the treatment of MDS. The study doctor can explain how the study drugs are designed to work. Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)
  • Official Title: Phase II Combination of Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

Clinical Trial IDs

  • ORG STUDY ID: 2014-0934
  • SECONDARY ID: NCI-2015-02120
  • NCT ID: NCT02599649

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
LirilumabHigh Risk MDS Group - Azacitidine + Lirilumab
NivolumabBMS-936558, OpdivoHigh Risk MDS Group - Azacitidine + Lirilumab + Nivolumab
Azacitidine5-azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, AzacytidineHigh Risk MDS Group - Azacitidine + Lirilumab

Purpose

The goal of this clinical research study is to learn if lirilumab and Opdivo (nivolumab), alone or in combination with Vidaza (azacitidine), can help to control MDS. The safety of these drug combinations will also be studied. This is an investigational study. Lirilumab is not FDA approved or commercially available. It is currently being used for research purposes. Nivolumab is FDA approved and commercially available for the treatment of melanoma and non small cell lung cancer (NSCLC). Azacitidine is FDA approved and commercially available for the treatment of MDS. The study doctor can explain how the study drugs are designed to work. Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Groups and Study Drug Administration:

      If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
      study groups based on the status of the disease and then you will be assigned to a cohort
      based on when you join this study. Each study group will be made up of 2 cohorts. Group 1 is
      made up of Cohorts A and B. Group 2 is made up of Cohorts C and D. Each cohort will enroll up
      to 20 participants each.

      Each study cycle is 4 weeks.

      If you have low risk (low or intermediate-1) MDS, you will be enrolled in Group 1.

        -  If you are assigned to Cohort A, you will receive lirilumab by vein over about 1 hour 1
           time each cycle.

        -  If you are assigned to Cohort B, you will receive nivolumab by vein over about 1 hour
           every 2 weeks during Cycles 1-9 and then 1 time each cycle after that. You will also
           receive lirilumab by vein over about 1 hour 1 time each cycle.

      If you have high risk MDS, you will be enrolled in Group 2.

        -  If you are assigned to Cohort C, you will receive azacitidine by vein for up to 40
           minutes on Days 1-7 of each cycle. You will also receive lirilumab by vein over about 1
           hour on Day 7 of each cycle.

        -  If you are assigned to Cohort D, you will receive azacitidine by vein for up to 40
           minutes on Days 1-7 of each cycle. You will receive lirilumab by vein over about 1 hour
           on Day 7 of each cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10
           and beyond, you will also receive nivolumab by vein over about 1 hour.

      If you are assigned to Cohorts B or D, you will need to stay in the clinic for up to 1 hour
      after your dose of nivolumab so the study staff may check your vitals and monitor your health
      for any side effects.

      Both you and the study doctor will know to which group you have been assigned.

      Study Visits:

      One (1) time each week during Cycle 1 and then 1 time during each 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 28 of Cycle 1 and then every 3 months after that,
      you will have a bone marrow aspiration to check the status of the disease and for cytogenetic
      testing.

      Every 6 weeks, if you can become pregnant, blood (about 1 teaspoon) or urine will be
      collected for a pregnancy test.

      Length of Study:

      You may continue receiving the study drug(s) as long as the study 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.

      You participation on this study, if you cannot become pregnant, will end after your last dose
      of study drug(s). If you can become pregnant, your participation on this study will be over
      after the follow-up pregnancy tests.

      Follow-Up Pregnancy Tests:

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

Trial Arms

NameTypeDescriptionInterventions
Low or Intermediate-1 MDS Group - LirilumabExperimentalLirilumab by vein over about 60 minutes 1 time each 28 day cycle.
  • Lirilumab
Low or Intermediate-1 MDS Group - Nivolumab + LirilumabExperimentalNivolumab by vein over about 60 minutes every 2 weeks during Cycles 1-9. Lirilumab by vein over about 60 minutes 1 time each cycle. Cycle is 28 days.
  • Lirilumab
  • Nivolumab
High Risk MDS Group - Azacitidine + LirilumabExperimentalAzacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle.
  • Lirilumab
  • Azacitidine
High Risk MDS Group - Azacitidine + Lirilumab + NivolumabExperimentalAzacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10 and beyond, Nivolumab by vein over about 60 minutes.
  • Lirilumab
  • Nivolumab
  • Azacitidine

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with MDS (up to 20% blasts) of any risk. Patients with lower risk MDS (low
             and int-1 by IPSS) could have received prior non-hypomethylating agent therapy (ie
             growth factors or lenalidomide). Patients with higher risk MDS (int-2 or high by IPSS)
             should not have received prior therapy with a hypomethylating agent.

          2. Age 18 years or older.

          3. Adequate organ function: creatinine </=2.5 x Upper Limit of Normal (ULN); serum
             bilirubin </=2.5 x ULN; aspartate transaminase (AST) and alanine transaminase (ALT)
             </=2.5 x ULN.

          4. Eastern Cooperative Oncology Group (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 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 drug. 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 for 31 weeks after the last dose of
             nivolumab.

          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
             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.

          4. Patients unwilling or unable to comply with the protocol.

          5. Patients who are on high dose steroid (ie prednisone or equivalent more than 10 mg a
             day) or immune suppression medications.

          6. Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive
             sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g.,
             Wegener's Granulomatosis]).

          7. Patients with a history of Inflammatory Bowel Disease such as Crohn's disease and
             ulcerative colitis

          8. 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) or with a history of HIV disease.

          9. Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational
             agents.

         10. Females who are pregnant or lactating

         11. Prior treatment with stem cell transplantation.

         12. Prohibited Prior Treatments and/or Therapies: a) Prior therapy with an anti-KIR,
             anti-PD-1, or anti-PD-L1, antibody. b) Prior treatment regimens with any immune cell
             modulating antibody such as anti-CD137 and anti-OX40. However, prior anti-CTLA4
             therapy is allowed if the last dose is 101 days or more from the first dose of study
             drug. c) Exposure to any other investigational drug within 2 weeks prior to the first
             dose of study drug (within 101 days for anti-CTLA4 therapy). d) Any anti-cancer
             therapy (e.g., chemotherapy, biologics, vaccines, radiotherapy with curative intent,
             or hormonal treatment) within 2 weeks prior to the first dose of study drug
             administration (within 101 days for anti-CTLA4 therapy administration.

         13. Continued from #12: e) Use of non-oncology vaccines containing live virus for
             prevention of infectious diseases within 4 weeks prior to study drug. The use of the
             inactivated seasonal influenza vaccine (Fluzone®) is allowed. f) Systemic
             corticosteroid at immunosuppressive doses (> 10 mg/day of prednisone or equivalent),
             must be discontinued at least 2 weeks prior to enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:116 days
Safety Issue:
Description:Overall response rate (ORR) defined as complete response plus partial response (CR + PR) and hematological improvement (HI). MDS International Working Group criteria used to assess response.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Myelodysplastic syndrome
  • MDS
  • Low or intermediate-1 MDS
  • High Risk MDS
  • Lirilumab
  • Nivolumab
  • BMS-936558
  • Opdivo
  • Azacitidine
  • 5-azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Azacytidine

Last Updated

January 14, 2020