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

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ClinicalTrials.gov Identifier: NCT03190733
Recruitment Status : Not yet recruiting
First Posted : June 19, 2017
Last Update Posted : June 19, 2017
Sponsor:
Collaborators:
Nanfang Hospital of Southern Medical University
First Affiliated Hospital, Sun Yat-Sen University
Second Affiliated Hospital, Sun Yat-Sen University
Information provided by (Responsible Party):
Zhujiang Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host-disease Leukemia Relapse Drug: ATG Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation
Estimated Study Start Date : August 30, 2017
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021


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.
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 Name: 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 Name: fludarabine




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. no relapse mortality one year [ Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation ]
    no relapse death



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Ages Eligible for Study:   14 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03190733


Contacts
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Contact: Jianghui xu, Dr 00862062782318 xiaoxu_75@sina.com

Sponsors and Collaborators
Zhujiang Hospital
Nanfang Hospital of Southern Medical University
First Affiliated Hospital, Sun Yat-Sen University
Second Affiliated Hospital, Sun Yat-Sen University
Investigators
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Principal Investigator: Bingyi Wu, MD Zhejiang Hospital of southern Medical Unversity

Publications:
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Responsible Party: Zhujiang Hospital
ClinicalTrials.gov Identifier: NCT03190733     History of Changes
Other Study ID Numbers: 2016-XYNK-001
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: June 19, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: individual participant data are to be shared with other researchers, when it will be available and be obtained by web.

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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

Keywords provided by Zhujiang Hospital:
Hematopoietic Stem Cell Transplantation
ATG
chronic GVHD
leukemia relapse

Additional relevant MeSH terms:
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Leukemia
Recurrence
Graft vs Host Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Immune System Diseases
Fludarabine
Thymoglobulin
Antilymphocyte Serum
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents