Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

St. Petersburg State Pavlov Medical University

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Thymoglobulin; Drug: Busulfan; Drug: Fludarabine monophosphate; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Procedure: Unrelated allogeneic stem cell transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT02627573

06/15-n

Details and patient eligibility

About

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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 2 patient groups

Thymoglobulin

Experimental group

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

Treatment:

Drug: Fludarabine monophosphate

Drug: Busulfan

Drug: Mycophenolate mofetil

Drug: Tacrolimus

Procedure: Unrelated allogeneic stem cell transplantation

Drug: Thymoglobulin

PTCy

Experimental group

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

Treatment:

Drug: Fludarabine monophosphate

Drug: Busulfan

Drug: Mycophenolate mofetil

Drug: Cyclophosphamide

Drug: Tacrolimus

Procedure: Unrelated allogeneic stem cell transplantation