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Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT

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ClinicalTrials.gov Identifier: NCT02294552
Recruitment Status : Completed
First Posted : November 19, 2014
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

Brief Summary:
This study evaluates the efficacy of high-dose post-transplantation cyclophosphomide as graft-versus-host disease (GVHD) prophylaxis after allogeneic stem cell transplantation in patients with different risk of GVHD. The risk-adapted strategy involves using single-agent cyclophosphomide in recipients of matched bone marrow graft, and combining cyclophosphomide with tacrolimus and mycophenolate mofetil in recipients of matched peripheral blood stem cells and mismatched bone marrow.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoid Leukemia Lymphoma Myelodysplastic Syndromes Chronic Lymphocytic Leukemia Immune System Diseases Drug: Cyclophosphamide Drug: Busulfan Drug: Fludarabine monophosphate Drug: Tacrolimus Drug: Mycophenolate mofetil Procedure: Allogeneic hematopoietic stem cell transplantation Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-dose Post-transplantation Cyclophosphamide as Graft Versus-host Disease Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : October 2014
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2017


Arm Intervention/treatment
Experimental: Matched bone marrow graft
Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv
Drug: Cyclophosphamide
Drug: Busulfan
Drug: Fludarabine monophosphate
Procedure: Allogeneic hematopoietic stem cell transplantation
Experimental: Matched peripheral blood stem cells graft
Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration
Drug: Cyclophosphamide
Drug: Busulfan
Drug: Fludarabine monophosphate
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Procedure: Allogeneic hematopoietic stem cell transplantation
Experimental: Mismatched peripheral blood stem cells or bone marrow graft
Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration
Drug: Cyclophosphamide
Drug: Busulfan
Drug: Fludarabine monophosphate
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Procedure: Allogeneic hematopoietic stem cell transplantation



Primary Outcome Measures :
  1. Incidence of acute and chronic GVHD, requiring treatment [ Time Frame: 365 days ]

Secondary Outcome Measures :
  1. Incidence of primary graft failure [ Time Frame: 60 days ]
  2. Non-relapse mortality analysis [ Time Frame: 365 days ]
  3. Overall survival analysis [ Time Frame: 365 days ]
  4. Event-free survival analysis [ Time Frame: 365 days ]
  5. Relapse rate analysis [ Time Frame: 365 days ]
  6. Toxicity based NCI CTC grades [ Time Frame: 100 days ]
  7. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [ Time Frame: 100 days ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have an indication for allogeneic hematopoietic stem cell transplantation
  • Signed informed consent
  • Patients with a donor available. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is required for related donor. A minimum match of 8/10 is required for unrelated donor.
  • No second tumors
  • No severe concurrent illness

Exclusion Criteria:

  • Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
  • Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
  • Respiratory distress >grade I
  • Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
  • Creatinine clearance < 60 mL/min
  • Uncontrolled bacterial or fungal infection at the time of enrollment
  • Requirement for vasopressor support at the time of enrollment
  • Karnofsky index <30%
  • Pregnancy
  • Somatic or psychiatric disorder making the patient unable to sign informed consent

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): NCT02294552


Locations
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Russian Federation
First Pavlov State Medical University of St. Petersburg
Saint-Petersburg, Russian Federation, 197089
Sponsors and Collaborators
Ivan S Moiseev
Investigators
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Principal Investigator: Boris V Afanasyev, MD, Prof. First Pavlov State Medical University of St. Petersburg

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ivan S Moiseev, Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier: NCT02294552     History of Changes
Other Study ID Numbers: PTCy-2014
First Posted: November 19, 2014    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Keywords provided by Ivan S Moiseev, St. Petersburg State Pavlov Medical University:
Cyclophosphamide
Leukemia
Lymphoma
Myelodysplastic Syndromes
Chronic Lymphocytic Leukemia
Immunosuppressive Agents
Immune System Diseases
Busulfan
Fludarabine
Tacrolimus
Mycophenolate mofetil
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Hematopoietic Stem Cell Transplantation
Allogeneic

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Immune System Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Cyclophosphamide
Tacrolimus
Fludarabine phosphate
Busulfan
Antineoplastic Agents, Alkylating
Fludarabine
Mycophenolic Acid
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents