Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02627573
• Other study ID #: 06/15-n
• Status: Terminated
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: April 3, 2019

Study information

• Verified date: April 2019
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: April 3, 2019
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Disease
• Leukemia
• Leukemia, Chronic Myeloid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Procedure:
• Unrelated allogeneic stem cell transplantation

Drug:
• Busulfan

• Fludarabine monophosphate

• Tacrolimus

• Mycophenolate mofetil

• Cyclophosphamide

• Thymoglobulin

Locations

Country	Name	City	State
Russian Federation	First Pavlov State Medical University of St. Petersburg	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of primary graft failure		60 days
Secondary	Incidence of acute GVHD, grades II-IV		365 days
Secondary	Incidence of chronic GVHD, moderate and severe (NIH criteria)		365 days
Secondary	Non-relapse mortality analysis		365 days
Secondary	Event-free survival analysis		365 days
Secondary	Overall survival analysis		365 days
Secondary	Relapse rate analysis		365 days
Secondary	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	100 days
Secondary	Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence		100 days