A Optimal Anti-Thymoglobuline (ATG) Dose Decrease cGVHD But Not Increase Leukemia Relapse for Haplo-HSCT

June 15, 2017 updated by: Zhujiang Hospital

A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation

In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients with acute leukemia (14~60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in fludarabine, busulfan, cyclophosphamide and antilymphocyte globulin (FBCA) pretreatment protocol of Haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The purpose is to compare the incidences of chronic graft vs host disease (cGVHD) in haplo-HSCT recipients receiving different dose ATG and one year leukemia relapse after transplantation. The main objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with haplo-HSCT.

Study Overview

Status

Unknown

Intervention / Treatment

Detailed Description

Human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation is an effective method for the treatment of hematological malignancies. However, high incidence rate of graft-versus-host disease (GVHD) seriously affects the quality of life of patients.

Using ATG in vivo T cell transplantation regimens reduce the rate of acute GVHD (aGVHD) and cGVHD. However, the optimal dose of ATG is unknown, Huang's reported that a prospective, randomized trial, which compared the long-term outcomes of 2 ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were received 10 mg/kg or 6 mg/kg of ATG in conditioning regimen. The 5-year cumulative incidence of cGVHD was found to be higher with ATG 6mg/kg (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]. ATG 10mg/kg in conditioning regimen was found to be associated with a lower risk of cGVHD. But the moderate-to-severe cGVHD was as high as 35%. We established the FBCA pretreatment regimen which added ATG and achieve the goal of reducing GVHD. In this FBCA pretreatment regimen the ATG dose was 12.5mg/kg which higher than that of other protocol. The cumulative incidence of grades II-IV aGVHD and cGVHD was 21.9% and 14.3% with the 12.5mg/kg ATG in the FBCA conditioning regimen which was lower than that of ATG 10mg/kg reported by Huang. However, ATG may lead to immunosuppression and lead to slow recovery of immune function and increased infection rate and may increase leukemia relapse after transplantation. What is the optimal does of ATG in FBCA pretreatment regimen which could reduce cGVHD and not increase leukemia relapse after transplantation? Access to ClinicalTrials and other sites found that there was still no related international studies with the FBCA conditioning regimen. We hypothesize that total ATG dose 12.5mg/kg in FBCA pretreatment regimen will decrease cGVHD and not increase leukemia relapse post transplantation.

In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients (14~60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in the FBCA pretreatment protocol of haploidentical hematopoietic stem cell transplantation. The purpose of this study is to compare the incidences of cGVHD and one year leukemia relapse in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis The first objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with HLA haploid hematopoietic stem cell transplantation.

Study Type

Interventional

Enrollment (Anticipated)

192

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 60 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. patients age between 14 yeas old and 60 years old
  2. patients with acute myeloid leukemia and acute lymphoblastic leukemia who needed stem cell transplantation without available HLA-identical related or unrelated donors

Exclusion Criteria:

  1. Patients with severe infections
  2. patients with major organ abnormal including renal, liver, lung or heart.
  3. Patients with any conditions not suitable for the trial (investigators' decision)
  4. patients age below 14 years old and more than 60 years old.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ATG 10.0mg/kg
ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg.
ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention.
Other Names:
  • fludarabine
ACTIVE_COMPARATOR: ATG 12.5mg/kg
ATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg.
ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention.
Other Names:
  • fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
occurrence of chronic GVHD
Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation
chronic GVHD diagnosis based on National Institutes of Health (NIH) criterion
from the day of stem cell transplantation to one year after stem cell transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
one year cumulative incidence of leukemia relapse
Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation
leukemia relapse base on morphology criterion
from the day of stem cell transplantation to one year after stem cell transplantation
The cumulative incidence rate of acute GVHD
Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation
acute GVHD diagnosis based on NIH criterion
from the day of stem cell transplantation to one year after stem cell transplantation
no relapse mortality one year
Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation
no relapse death
from the day of stem cell transplantation to one year after stem cell transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Bingyi Wu, MD, Zhejiang Hospital of southern Medical Unversity

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

August 30, 2017

Primary Completion (ANTICIPATED)

September 30, 2020

Study Completion (ANTICIPATED)

September 30, 2021

Study Registration Dates

First Submitted

June 15, 2017

First Submitted That Met QC Criteria

June 15, 2017

First Posted (ACTUAL)

June 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 19, 2017

Last Update Submitted That Met QC Criteria

June 15, 2017

Last Verified

December 1, 2016

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

individual participant data are to be shared with other researchers, when it will be available and be obtained by web.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leukemia Relapse

Clinical Trials on ATG

Subscribe