ATG/PTCy in Haplo-PBSCT Randomized Controlled,Multi-center (ATG/PTCy)

October 4, 2023 updated by: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai General Hospital Affiliated to Shanghai Jiao Tong University

A novel regimen, which is composed of a low dose of ATG (5 mg/kg) and low-dose PTCy (one dose of PTCy, 50mg/kg) for GvHD prophylaxis in Haplo-PBSCT for patients with hematologic malignancies, was designed to decrease the risk of aGvHD and lower the incidence of virus reactivation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute graft-versus-host disease (aGvHD) is the most important obstacle of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for treatment of patients with hematologic malignancies. In the last two decades, the results of Haplo-HSCT have been conspicuously improved due to effective prophylaxis strategies for aGvHD, such as in vivo T cell depletion (TCD) with anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy).

The regimens for prophylaxis of GvHD based on rabbit anti-human thymocyte immunoglobin (ATG 10mg/kg, Thymoglobin®, Genzyme Polyclonals S.A.S) effectively prevented the occurrence of grade II-IV aGvHD with an incidence of 33.4%-46%, grade III-IV aGvHD 12%-14.9%, but the reactivation incidences of cytomegalovirus (CMV) and EB virus (EBV) were higher due to a slower immune reconstitution(2-4). The 100-day CIs of CMV and EBV viremia were 61%-64%and over 50%, respectively. Although ATG-based regimens have achieved excellent results, the incidences of aGvHD and the post-transplant virus reactivation are still higher, affecting the long-term survival of the patients.

The regimen of PTCy for prevention of GvHD was developed in 1999 by St. Johns Hopkin's group in Baltimore (1) and had outstanding results with the CIs of 34% grades II-IV and of 6% grades III-IV aGvHD by day 200 in haplo-bone marrow transplantation (Haplo-BMT) (7), respectively. The incidences of viral and fungal infection in Haplo-HSCT with PTCy for GvHD prophylaxis were much lower than ATG based regimens. Ruggeri A（8）et al retrospectively analyzed the effects of different stem cell source (BM vs PBSC) on the transplant results in Haplo-HSCT with PTCy. The results showed that BM was associated with a lower incidence of grades II-IV and grades III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively), which was further confirmed by Bashey A et al' study（9）. These data indicated that PTCy regimen don't have the same effects for GvHD prophylaxis with PBSC graft as compared with BM graft in Haplo-HSCT.

A novel regimen, which is composed of a low dose of ATG (5 mg/kg) and low-dose PTCy (one dose of PTCy, 50mg/kg) for GvHD prophylaxis in Haplo-PBSCT for patients with hematologic malignancies, was designed to decrease the risk of aGvHD and lower the incidence of virus reactivation. A prospective, phase II clinical trial (Clinicaltrials.org NCT03395860) was performed to evaluate the efficacy with low dose ATG followed by low dose PTCy as GvHD prophylaxis.Thirty-two patients diagnosed with hematological malignancies were enrolled in this trial. All patients received myeloablative conditioning regimens except for three patients. The cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD were 19.4% (95% CI, 5.5-33.3%) and 6.9% (95% CI 0-16.3%) by day 100, respectively. The one-year probability of relapse was 25.1% (95% CI, 7.3-42.9%). The one-year probabilities of disease free-survival (DFS) and overall survival (OS) was 59% (95% CI, 33.3%-84.7%) and 78.4% (95% CI, 63%-93.8%), respectively. The CIs of CMV reactivation and EBV reactivation by day 180 were 37.5% (95% CI, 19.8-55.2%) and 40.6% (95% CI, 22.6-58.6%), respectively. The results suggested that low dose ATG with low dose PTCy as GvHD prophylaxis in Haplo-PBSCT had promising activity. A prospective randomized trial is required to compare the efficacies of this regimen with ATG-based or PTCy-based regiments in Haplo-PBSCT.

Study Type

Interventional

Enrollment (Actual)

418

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 Locations

  • China
      • Shanghai, China
        • Shanghai Tongji Hospital
    • Shandong
      • Qinan, Shandong, China
        • General Hospital of Jinan Military Command.
    • Shanghai
      • Shanghai, Shanghai, China, 200002
        • Shanghai Ruijin Hospital, affiliated with the Medical School of Shanghai Jiaotong University,
      • Shanghai, Shanghai, China, 200080
        • Changhai Hospital
      • Shanghai, Shanghai, China, 200080
        • Xianmin Song
      • Shanghai, Shanghai, China
        • Shanghai Xinghua Hospital, affiliated with the Medical School of Shanghai Jiaotong University,

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 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Clinical diagnosis of hematologic malignancies (AML CR/blast cell≤20% high-risk MDS) were enrolled in this study. Diagnosis was according to the criteria of 2008 World Health Organization (WHO) classification of myeloid tumors.
  2. Family members selected as donors were typed at the HLA-A, -B, -DQB1, -C and -DRB1 locus at high-resolution level. Haplotype was defined as recipient-donor number of HLA mismatches > 3.

3.14 to 70 years old. 4.Performance status scores no more than 2 (ECOG criteria). 5.Adequate organ function as defined by the following criteria: alanine transaminase （ALT）, aspartate transaminase（AST） and total serum bilirubin <2×ULN (upper limit of normal). Serum creatinine and blood urea nitrogen (BUN) <1.25×ULN.

6.Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation(the patients has been improved after treatment of the disease and are not expected to affect transplant can include in the study).

7.Absence of any other contraindications of stem cell transplantation. Willingness and ability to perform HSCT.

8.Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. DSA strong positive (titer >10000MFI)
  2. Life expectancy < 3 months because of other severe diseases.
  3. Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure.
  4. Uncontrolled infection.
  5. Pregnancy or breastfeeding.
  6. Has enrolled in another clinical trials.
  7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATG/PTCy
The GvHD prophylaxis consisted of ATG 2.5mg/kg administered on day -2 to -1 and cyclophosphamide (Cy) 50 mg/kg on day +3, cyclosporine A (CsA) and mycophenolate mofetil (MMF) initiating on day +4. CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 3 times per day (maximum dose 3g per day) until day +34 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.
Drug: ATG/PTCy
low dose Antithymocyte Globulin plus low dose post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation
Active Comparator: standard ATG
The GvHD prophylaxis consisted of ATG 2.5mg/kg administered on day -4 to -1 , cyclosporine A (CsA) initiating on day -5 and mycophenolate mofetil (MMF) initiating on day +1 . CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 2 times per day (maximum dose 2g per day) until day +30 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.
Drug: standard ATG
in vivo T cell depletion (TCD) with anti-thymocyte globulin (ATG) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation
Other Names:
  • ATG
Active Comparator: standard PTCy
The GvHD prophylaxis consisted of cyclophosphamide (Cy) 50 mg/kg on day +3, +4,cyclosporine A (CsA) and mycophenolate mofetil (MMF) initiating on day +5. CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 3 times per day (maximum dose 3g per day) until day +35 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.
Drug: standard PTCy
post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell
Other Names:
  • PTCy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The cumulative incidences of acute GVHD
Time Frame: 100 days after transplantation
The cumulative incidences of aGvHD was defined as the number and the ratio of the participants with aGVHD
100 days after transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: 2 years
overall survival
2 years
Leukocyte engraftment
Time Frame: 1 month
Leukocyte engraftment:(was defined as the first of three consecutive days of peripheral white blood count >1000/ul.
1 month
Platelet engraftment
Time Frame: 1 month
Platelet engraftment:(was defined as the first of seven consecutive days of platelet counts of >20000/ul.
1 month
Donor chimerism
Time Frame: 2 years
Quantitative chimerism analyzes were performed using short-tandem-repeat-based polymerase chain reaction technique sat regular intervals for every 4 weeks after allografting in bone marrow.
2 years
Relapse incidence (RI)
Time Frame: 2 YEARS]
RI was defined as the number and ratio of the participants with relapse after transplantation
2 YEARS]
chronic GVHD
Time Frame: 2 years
cGvHD was diagnosed and graded according to the 2014 National Institutes of Health (NIH) consensus criteria: mild, moderate or severe respectively.The number and ratio of participants with cGVHD after transplatation
2 years
infection
Time Frame: 2 years
CMV and EB infections(The number and ration of participants with infection after transplantaton)
2 years
DFS
Time Frame: 2 years
disease free survival
2 years

Collaborators and Investigators

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

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

  • Study Chair: xinpeng wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

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 (Actual)

July 28, 2018

Primary Completion (Actual)

August 23, 2023

Study Completion (Actual)

August 23, 2023

Study Registration Dates

First Submitted

July 28, 2018

First Submitted That Met QC Criteria

July 28, 2018

First Posted (Actual)

July 31, 2018

Study Record Updates

Last Update Posted (Actual)

October 5, 2023

Last Update Submitted That Met QC Criteria

October 4, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • SHSYXY-ATG/PTCy multi-center

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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 Myeloid Tumor

Clinical Trials on ATG/PTCy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe