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Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

Primary Purpose

Leukemia, Chronic Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Status
Terminated
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Unrelated allogeneic stem cell transplantation
Busulfan
Fludarabine monophosphate
Tacrolimus
Mycophenolate mofetil
Cyclophosphamide
Thymoglobulin
Sponsored by
St. Petersburg State Pavlov Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Leukemia, Chronic Myeloid focused on measuring Cyclophosphamide, Thymoglobulin, Myelodysplastic Syndromes, Immunosuppressive Agents, Immune System Diseases, Busulfan, Fludarabine, Tacrolimus, Mycophenolate mofetil, Antineoplastic Agents, Alkylating, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic Transplantation, Leukemia, Chronic Myeloid, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have an indication for allogeneic hematopoietic stem cell transplantation
  • Diagnosis: Chronic myeloid leukemia Myelodysplastic Syndromes Myeloprolipherative neoplsm unclassified Atypical chronic myelogenous leukemia
  • Signed informed consent
  • Patients with 10/10 HLA-matched unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. Mismatches in these loci are not allowed.
  • Peripheral blood stem cells as graft source
  • No second tumors
  • No prior history of Thymoglobulin exposure or no history of anaphylactic shock after Thymoglobulin administration
  • 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 Type

Experimental

Experimental

Arm Label

Thymoglobulin

PTCy

Arm Description

Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -5 Busulfan 1 mg/kg po qid x 2 days Days -4 through -3 Thymoglobulin 2,5 mg/kg po qd x 2 days Days -1 through +30: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days -1 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration

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

Outcomes

Primary Outcome Measures

Incidence of primary graft failure

Secondary Outcome Measures

Incidence of acute GVHD, grades II-IV
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Non-relapse mortality analysis
Event-free survival analysis
Overall survival analysis
Relapse rate analysis
Toxicity (NCI CTCAE 4.03)
Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

Full Information

First Posted
December 4, 2015
Last Updated
April 3, 2019
Sponsor
St. Petersburg State Pavlov Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT02627573
Brief Title
Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT
Official Title
Randomized Trial of GVHD Prophylasxis With Post-transplantation Cyclophocphomide (PTCy) or Thymoglobulin in Unrelated SCT Recepients With Chronic Myeloproliferative Neoplasms and Myelodisplatic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Poor recruitment
Study Start Date
July 2015 (Actual)
Primary Completion Date
April 3, 2019 (Actual)
Study Completion Date
April 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Petersburg State Pavlov Medical University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Purpose There is a growing evidence of high efficacy of post-transplantation cyclophocphomide (PTCy)-based GVHD prophylaxis in haploidentical and matched related and unrelated bone marrow transplantation. There is limitted, but growing data on safety and efficacy of this prophylaxis in unrelated and peripheral blood stem cell transplantations. Use of PTCy in chronic myeloproliferative neoplasms and myelodisplatic syndrome is of particular interest. On the one hand, PTCy could reduce the incidence of chronic GVHD and long-term bormidity. On the other hand, there is a concern, that PTCy can increase the incidence of graft failures in this group of patients. Currently published data indicate that low-dose Thymoglobulin-based prophylaxis is the most promissing compatitor in terms of acute and chronic GVHD control. So there is a rationale to randomize Thymoglobulin and PTCy as GVHD prophilaxis. Pre-transplant assesment of moratlity (PAM)-index will be used as the strata for randomization, as it is the paramter that takes into account the most important factors effecting survival. The conditioning regimen and the other two components of GVHD prophylaxis (mycophenolate mofetil and tacrolimus) will be identical in the two arms of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Chronic Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Keywords
Cyclophosphamide, Thymoglobulin, Myelodysplastic Syndromes, Immunosuppressive Agents, Immune System Diseases, Busulfan, Fludarabine, Tacrolimus, Mycophenolate mofetil, Antineoplastic Agents, Alkylating, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic Transplantation, Leukemia, Chronic Myeloid, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thymoglobulin
Arm Type
Experimental
Arm Description
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -5 Busulfan 1 mg/kg po qid x 2 days Days -4 through -3 Thymoglobulin 2,5 mg/kg po qd x 2 days Days -1 through +30: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days -1 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
Arm Title
PTCy
Arm Type
Experimental
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Unrelated allogeneic stem cell transplantation
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
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
Thymoglobulin
Primary Outcome Measure Information:
Title
Incidence of primary graft failure
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Incidence of acute GVHD, grades II-IV
Time Frame
365 days
Title
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Time Frame
365 days
Title
Non-relapse mortality analysis
Time Frame
365 days
Title
Event-free survival analysis
Time Frame
365 days
Title
Overall survival analysis
Time Frame
365 days
Title
Relapse rate analysis
Time Frame
365 days
Title
Toxicity (NCI CTCAE 4.03)
Description
Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy
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
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have an indication for allogeneic hematopoietic stem cell transplantation Diagnosis: Chronic myeloid leukemia Myelodysplastic Syndromes Myeloprolipherative neoplsm unclassified Atypical chronic myelogenous leukemia Signed informed consent Patients with 10/10 HLA-matched unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. Mismatches in these loci are not allowed. Peripheral blood stem cells as graft source No second tumors No prior history of Thymoglobulin exposure or no history of anaphylactic shock after Thymoglobulin administration 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, Professor
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

Plan to Share IPD
No

Learn more about this trial

Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

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