Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

NCT ID: NCT02627573

Last Updated: 2019-04-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2019-04-03

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Thymoglobulin

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

Group Type: EXPERIMENTAL

Unrelated allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Busulfan

Intervention Type: DRUG

Fludarabine monophosphate

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Mycophenolate mofetil

Intervention Type: DRUG

Thymoglobulin

Intervention Type: DRUG

PTCy

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

Group Type: EXPERIMENTAL

Unrelated allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Busulfan

Intervention Type: DRUG

Fludarabine monophosphate

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Mycophenolate mofetil

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Interventions

Unrelated allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Busulfan

Intervention Type: DRUG

Fludarabine monophosphate

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Mycophenolate mofetil

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Thymoglobulin

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ivan S Moiseev

Head of adolescent and adult department of oncology, heamatology and transplantation

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Boris V. Afanasyev, Professor

Role: PRINCIPAL_INVESTIGATOR

First Pavlov State Medical University of St. Petersburg

Locations

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, , Russia

Countries

Russia

Other Identifiers

06/15-n

Identifier Type: -

Identifier Source: org_study_id