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
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
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 |

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:
|
- 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.
- 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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
Russian Federation | |
First Pavlov State Medical University of St. Petersburg | |
Saint-Petersburg, Russian Federation, 197089 |
Responsible Party: | Ivan S Moiseev, Vice-director for science, R.M. Gorbacheva memorial institute, St. Petersburg State Pavlov Medical University |
ClinicalTrials.gov Identifier: | NCT03259516 |
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 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
myelodysplastic syndrome nivolumab 5-azacitidine cytarabine |
melphalan all-trans retinoic acid lymphodepletion |
Preleukemia Myelodysplastic Syndromes Nivolumab Syndrome Disease Pathologic Processes Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Neoplasms Cytarabine Cyclophosphamide 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 Immune Checkpoint Inhibitors Antimetabolites, Antineoplastic Antimetabolites |