Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nivolumab With Chemotherapy in Refractory MDS

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: NCT03259516
Recruitment Status : Terminated (Slow recruitment rate)
First Posted : August 23, 2017
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

Tracking Information
First Submitted Date  ICMJE August 22, 2017
First Posted Date  ICMJE August 23, 2017
Last Update Posted Date April 5, 2019
Actual Study Start Date  ICMJE May 25, 2017
Actual Primary Completion Date December 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
Overall response rate [ Time Frame: 6 months ]
Overall response rate (ORR) defined as complete response plus partial response (CR + PR) and hematological improvement (HI). MDS International Working Group criteria will be used to assess response.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
  • Treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 6 months ]
    Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).
  • Infectious complications [ Time Frame: 6 months ]
    Incidence of severe bacterial, fungal and viral infections incidence based on laboratory confirmation and attending physician assessment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab With Chemotherapy in Refractory MDS
Official Title  ICMJE Pilot Open-label Trial of Nivolumab Combined With Chemotherapy in Refractory Myelodysplastic Syndromes.
Brief Summary There is evidence of involvement of checkpoint pathways, including PD-1, in the pathogenesis and resistance of myelodysplastic syndrome (MDS). However monotherapy with checkpoint inhibitors was ineffective in a number of studies, indicating the presence of several mechanisms of resistance. This pilot study evaluates the safety and preliminary efficacy of nivolumab combination with currently existing treatments in MDS patients who failed at least one line of therapy. The study evaluates if there is a combination which induces objective responses.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: Nivolumab
    1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
    Other Name: Opdivo
  • Drug: Azacitidine
    75 mg/m2 subcutaneously on Days 1-7 of a 28 day cycle
    Other Names:
    • 5-azacitidine
    • Vidaza
  • Drug: Fludarabine
    25 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle. Dose reduction to 15 mg/m2 is permitted in cases of grade 4 hematological toxicity after first cycle.
  • Drug: Cyclophosphamide
    300 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle.
  • Drug: Cytarabine
    10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle
    Other Name: Ara-C, LDAC
  • Drug: all trans retinoic acid
    45 mg/m2 per os daily during the whole course of treatment
    Other Name: ATRA
  • Drug: Sildenafil
    20 mg per os three times a day during the whole course of treatment
  • Drug: Melphalan
    2 mg per os daily during the whole course of treatment
Study Arms  ICMJE
  • Experimental: Nivo + FC
    Nivolumab 1 mg/kg days 1,15 iv q28days Fludarabine 25 mg/m2 days 1-3 iv q28days Cyclophosphamide 300 mg/m2 days 1-3 iv q28days
    Interventions:
    • Drug: Nivolumab
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Nivo + LDAC + ATRA
    Nivolumab 1 mg/kg days 1,15 iv q28days Cytarabine 10 mg/m2 bid days 1-10 sc q28days All-trans retinoic acid (ATRA) 45 mg/m2 po qd
    Interventions:
    • Drug: Nivolumab
    • Drug: Cytarabine
    • Drug: all trans retinoic acid
  • Experimental: Nivo + LDAC + Sildenafil
    Nivolumab 1 mg/kg days 1,15 iv q28days Cytarabine 10 mg/m2 bid days 1-10 sc q28days Sildenafil 20 mg tid
    Interventions:
    • Drug: Nivolumab
    • Drug: Cytarabine
    • Drug: Sildenafil
  • Experimental: Nivo + Melphalan
    Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days
    Interventions:
    • Drug: Nivolumab
    • Drug: Melphalan
  • Experimental: Nivo + 5-aza
    Nivolumab 1 mg/kg days 1,15 iv q28days 5-azacitidine 75 mg/m2 days 1-7 q28days
    Interventions:
    • Drug: Nivolumab
    • Drug: Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 3, 2019)
2
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2017)
50
Actual Study Completion Date  ICMJE December 25, 2018
Actual Primary Completion Date December 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with myelodysplastic syndrome (MDS) (up to 20% blasts) of any risk. Patients with lower risk MDS (low and int-1 by IPSS) should have failed prior non-hypomethylating agent therapy (ie growth factors or lenalidomide). Patients with higher risk MDS (int-2 or high by IPSS) should have failed prior at least one therapy with a hypomethylating agent or Ara-C.
  • Age 18 years or older.
  • No severe organ dysfunction: creatinine <=2.5 x ULN; serum bilirubin <=2.5 x ULN; AST and ALT <=5 x ULN.
  • Karnofsky index >=70%
  • 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 24 weeks
  • Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 24 weeks after the last dose of nivolumab.

Exclusion Criteria:

  • Another malignancy requiring treatment at the time of inclusion
  • History of interstitial lung disease or pneumonitis
  • 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
  • Active, known or suspected autoimmune disease requiring treatment at the time of inclusion
  • Pregnancy or breastfeeding
  • Patients unwilling or unable to comply with the protocol
  • Somatic or psychiatric disorder making the patient unable to sign informed consent
  • Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA4 therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03259516
Other Study ID Numbers  ICMJE 18/17-n
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ivan S Moiseev, St. Petersburg State Pavlov Medical University
Study Sponsor  ICMJE St. Petersburg State Pavlov Medical University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account St. Petersburg State Pavlov Medical University
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP