Nivolumab With Chemotherapy in Refractory MDS
Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring myelodysplastic syndrome, nivolumab, 5-azacitidine, cytarabine, melphalan, all-trans retinoic acid, lymphodepletion
Eligibility Criteria
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
Sites / Locations
- First Pavlov State Medical University of St. Petersburg
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Nivo + FC
Nivo + LDAC + ATRA
Nivo + LDAC + Sildenafil
Nivo + Melphalan
Nivo + 5-aza
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
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
Nivolumab 1 mg/kg days 1,15 iv q28days Cytarabine 10 mg/m2 bid days 1-10 sc q28days Sildenafil 20 mg tid
Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days
Nivolumab 1 mg/kg days 1,15 iv q28days 5-azacitidine 75 mg/m2 days 1-7 q28days