Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

NCT02627573 | Terminated Phase 2 DMC

• 1 other identifier: 06/15-n
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• Incidence of primary graft failure

  60 days

Secondary Outcomes (8)

• Incidence of acute GVHD, grades II-IV

  365 days

• Incidence of chronic GVHD, moderate and severe (NIH criteria)

  365 days

• Non-relapse mortality analysis

  365 days

• Event-free survival analysis

  365 days

• Overall survival analysis

  365 days

Study Arms (2)

Thymoglobulin

EXPERIMENTAL

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

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

PTCy

EXPERIMENTAL

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

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

Interventions

Unrelated allogeneic stem cell transplantation PROCEDURE

PTCy; Thymoglobulin

Busulfan DRUG

PTCy; Thymoglobulin

Fludarabine monophosphate DRUG

PTCy; Thymoglobulin

Tacrolimus DRUG

PTCy; Thymoglobulin

Mycophenolate mofetil DRUG

PTCy; Thymoglobulin

Cyclophosphamide DRUG

PTCy

Thymoglobulin DRUG

Thymoglobulin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Immune System Diseases

Interventions

Busulfan; fludarabine phosphate; Tacrolimus; Mycophenolic Acid; Cyclophosphamide; thymoglobulin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Boris V. Afanasyev, Professor

  First Pavlov State Medical University of St. Petersburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of adolescent and adult department of oncology, heamatology and transplantation

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: December 11, 2015
• Study Start: July 1, 2015
• Primary Completion: April 3, 2019
• Study Completion: April 3, 2019
• Last Updated: April 5, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)