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Trial record 4 of 14 for:    nivolumab | MDS

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

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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Nivolumab Drug: Azacitidine Drug: Fludarabine Drug: Cyclophosphamide Drug: Cytarabine Drug: all trans retinoic acid Drug: Sildenafil Drug: Melphalan Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Open-label Trial of Nivolumab Combined With Chemotherapy in Refractory Myelodysplastic Syndromes.
Actual Study Start Date : May 25, 2017
Actual Primary Completion Date : December 25, 2018
Actual Study Completion Date : December 25, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
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
Drug: Nivolumab
1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
Other Name: Opdivo

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.

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
Drug: Nivolumab
1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
Other Name: Opdivo

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

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
Drug: Nivolumab
1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
Other Name: Opdivo

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: Sildenafil
20 mg per os three times a day during the whole course of treatment

Experimental: Nivo + Melphalan
Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days
Drug: Nivolumab
1 mg/kg by vein on Days 1 and 15 of a 28 day cycle
Other Name: Opdivo

Drug: Melphalan
2 mg per os daily during the whole course of treatment

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. Infectious complications [ Time Frame: 6 months ]
    Incidence of severe bacterial, fungal and viral infections incidence based on laboratory confirmation and attending physician assessment



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259516


Locations
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Russian Federation
First Pavlov State Medical University of St. Petersburg
Saint-Petersburg, Russian Federation, 197089
Sponsors and Collaborators
St. Petersburg State Pavlov Medical University

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Responsible Party: Ivan S Moiseev, Vice-director for science, R.M. Gorbacheva memorial institute, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier: NCT03259516     History of Changes
Other Study ID Numbers: 18/17-n
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ivan S Moiseev, St. Petersburg State Pavlov Medical University:
myelodysplastic syndrome
nivolumab
5-azacitidine
cytarabine
melphalan
all-trans retinoic acid
lymphodepletion

Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Preleukemia
Nivolumab
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Cytarabine
Melphalan
Fludarabine
Azacitidine
Tretinoin
Sildenafil Citrate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites