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Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Cyclophosphamide
Busulfan
Fludarabine monophosphate
Tacrolimus
Mycophenolate mofetil
Allogeneic hematopoietic stem cell transplantation
Sponsored by
Ivan S Moiseev
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring 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

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • First Pavlov State Medical University of St. Petersburg

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Matched bone marrow graft

Matched peripheral blood stem cells graft

Mismatched peripheral blood stem cells or bone marrow graft

Arm Description

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 -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

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

Outcomes

Primary Outcome Measures

Incidence of acute and chronic GVHD, requiring treatment

Secondary Outcome Measures

Incidence of primary graft failure
Non-relapse mortality analysis
Overall survival analysis
Event-free survival analysis
Relapse rate analysis
Toxicity based NCI CTC grades
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

Full Information

First Posted
October 30, 2014
Last Updated
January 12, 2018
Sponsor
Ivan S Moiseev
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1. Study Identification

Unique Protocol Identification Number
NCT02294552
Brief Title
Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT
Official Title
High-dose Post-transplantation Cyclophosphamide as Graft Versus-host Disease Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
October 2014 (Actual)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ivan S Moiseev

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Lymphoma, Myelodysplastic Syndromes, Chronic Lymphocytic Leukemia, Immune System Diseases
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Matched bone marrow graft
Arm Type
Experimental
Arm Description
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
Arm Title
Matched peripheral blood stem cells graft
Arm Type
Experimental
Arm Description
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
Arm Title
Mismatched peripheral blood stem cells or bone marrow graft
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Type
Drug
Intervention Name(s)
Fludarabine monophosphate
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Intervention Type
Procedure
Intervention Name(s)
Allogeneic hematopoietic stem cell transplantation
Primary Outcome Measure Information:
Title
Incidence of acute and chronic GVHD, requiring treatment
Time Frame
365 days
Secondary Outcome Measure Information:
Title
Incidence of primary graft failure
Time Frame
60 days
Title
Non-relapse mortality analysis
Time Frame
365 days
Title
Overall survival analysis
Time Frame
365 days
Title
Event-free survival analysis
Time Frame
365 days
Title
Relapse rate analysis
Time Frame
365 days
Title
Toxicity based NCI CTC grades
Time Frame
100 days
Title
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Time Frame
100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boris V Afanasyev, MD, Prof.
Organizational Affiliation
First Pavlov State Medical University of St. Petersburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
First Pavlov State Medical University of St. Petersburg
City
Saint-Petersburg
ZIP/Postal Code
197089
Country
Russian Federation

12. IPD Sharing Statement

Citations:
PubMed Identifier
29360184
Citation
Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bykova TA, Chukhlovin AB, Pevtcov DE, Bondarenko SN, Afanasyev BV. Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018 May;100(5):395-402. doi: 10.1111/ejh.13030. Epub 2018 Mar 1.
Results Reference
derived

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Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT

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