Nivolumab With Chemotherapy in Refractory MDS

NCT ID: NCT03259516

Last Updated: 2019-04-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-25
• Study Completion Date: 2018-12-25

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Fludarabine

Intervention Type: 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

Intervention Type: DRUG

300 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle.

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Cytarabine

Intervention Type: DRUG

10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle

all trans retinoic acid

Intervention Type: DRUG

45 mg/m2 per os daily during the whole course of treatment

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Cytarabine

Intervention Type: DRUG

10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle

Sildenafil

Intervention Type: DRUG

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

Nivo + Melphalan

Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Melphalan

Intervention Type: DRUG

2 mg per os daily during the whole course of treatment

Nivo + 5-aza

Nivolumab 1 mg/kg days 1,15 iv q28days 5-azacitidine 75 mg/m2 days 1-7 q28days

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Azacitidine

Intervention Type: DRUG

75 mg/m2 subcutaneously on Days 1-7 of a 28 day cycle

Interventions

Nivolumab

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

Intervention Type: DRUG

Azacitidine

75 mg/m2 subcutaneously on Days 1-7 of a 28 day cycle

Intervention Type: 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.

Intervention Type: DRUG

Cyclophosphamide

300 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle.

Intervention Type: DRUG

Cytarabine

10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle

Intervention Type: DRUG

all trans retinoic acid

45 mg/m2 per os daily during the whole course of treatment

Intervention Type: DRUG

Sildenafil

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

Intervention Type: DRUG

Melphalan

2 mg per os daily during the whole course of treatment

Intervention Type: DRUG

Other Intervention Names

Opdivo; 5-azacitidine; Vidaza; Ara-C, LDAC; ATRA

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ivan S Moiseev

Vice-director for science, R.M. Gorbacheva memorial institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, , Russia

Countries

Russia

Other Identifiers

18/17-n

Identifier Type: -

Identifier Source: org_study_id