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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
192

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: ATG 10.0mg/kg
ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg.
Drug: ATG
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.
Drug: ATG
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhujiang Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
First Affiliated Hospital, Sun Yat-Sen University
Nanfang Hospital of Southern Medical University
Second Affiliated Hospital, Sun Yat-Sen University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2016-XYNK-001

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.

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