Clinical trial NCT02627573: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2015-12-11
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Incidence of primary graft failure
timeFrame: 60 days
Secondary outcomes:
measure: Incidence of acute GVHD, grades II-IV
timeFrame: 365 days
measure: Incidence of chronic GVHD, moderate and severe (NIH criteria)
timeFrame: 365 days
measure: Non-relapse mortality analysis
timeFrame: 365 days
measure: Event-free survival analysis
timeFrame: 365 days
measure: Overall survival analysis
timeFrame: 365 days
measure: Relapse rate analysis
timeFrame: 365 days
measure: Toxicity (NCI CTCAE 4.03)
timeFrame: 100 days
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: 100 days
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: First Pavlov State Medical University of St. Petersburg
name: Boris V. Afanasyev, Professor
role: PRINCIPAL_INVESTIGATOR
References: