Nivolumab With Chemotherapy in Refractory MDS

Sponsor
St. Petersburg State Pavlov Medical University
Study ID
NCT03259516
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

  • Myelodysplastic Syndromes

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
  • Azacitidine — DRUG
    75 mg/m2 subcutaneously on Days 1-7 of a 28 day cycle
  • Fludarabine — DRUG
    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.
  • Cyclophosphamide — DRUG
    300 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle.
  • Cytarabine — DRUG
    10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle
  • all trans retinoic acid — DRUG
    45 mg/m2 per os daily during the whole course of treatment
  • Sildenafil — DRUG
    20 mg per os three times a day during the whole course of treatment
  • Melphalan — DRUG
    2 mg per os daily during the whole course of treatment

Study Details

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.

Key Dates

Start date
May 25, 2017
Status verified
Apr 2019
Primary completion
Dec 25, 2018
Completion
Dec 25, 2018

Study Design

Enrollment
2 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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
  • 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
  • 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
  • Experimental: Nivo + Melphalan
    Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days
  • Experimental: Nivo + 5-aza
    Nivolumab 1 mg/kg days 1,15 iv q28days 5-azacitidine 75 mg/m2 days 1-7 q28days

Primary Outcome Measure

Overall response rate [ Time Frame: 6 months ]

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