Clinical trial NCT03259516: Nivolumab With Chemotherapy in Refractory MDS
Official title: Pilot Open-label Trial of Nivolumab Combined With Chemotherapy in Refractory Myelodysplastic Syndromes.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: myelodysplastic syndrome
nivolumab
5-azacitidine
cytarabine
melphalan
all-trans retinoic acid
lymphodepletion
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2017-08-23
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall response rate
timeFrame: 6 months
Secondary outcomes:
measure: Treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 6 months
measure: Infectious complications
timeFrame: 6 months
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
References: