Efficacy and Safety Study of ATG for Prophylaxis of aGVHD in Matched Sibling Donor PBSCT

Phase 4

Completed

• Conditions: aGVHD
• Interventions: Drug: ATG; Drug: CsA; Drug: mycophenolate mofetil; Drug: Methotrexate

• Registration Number: NCT02677181
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

The purpose of this study is to determine the efficacy and safety of combined ATG （antithymocyte globulin ） regimen for aGVHD(acute graft-versus-host disease ) prophylaxis in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT).

Detailed Description

Transplantation with G-CSF （Granulocyte colony stimulating factor ）mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with matched sibling donor transplantation. Unmanipulated haploidentical donor PBSCT (haplo-PBSCT) has been applied in patients with hematologic malignancies. In our previous cohort study, haplo-PBSCT was associated with lower incidence of severe acute GVHD and extensive chronic GVHD compared with matched sibling donor PBSCT (MSD-PBSCT). Haplo-PBSCT has the same GVHD prophylaxis regimen with MSD-PBSCT, except ATG. It suggested the potential advantage of ATG in prophylaxis of GVHD and improvement of long-term quality of life of the transplant recipients, which motivate us to observe the efficacy of combined ATG regimen for GVHD prophylaxis in MSD-PBSCT.

Study Timeline

• Study First Submitted: 2015-12-01
• Study Start: 2016-01
• Study First Submitted QC: 2016-02-04
• Study First Posted: 2016-02-09
• Primary Completion: 2020-01
• Study Completion: 2022-04
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-23
• Last Update Posted: 2022-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. acute myeloid leukemia (AML) in CR1 (complete remission 1) or CR2 (complete remission 2) phase regardless of cytogenetics;
2. CML CP(chronic myelogenous leukemia , chronic phase); NHL (non-Hodgkin's lymphoma )
3. MDS-RAEB(myelodysplastic syndrome -refractory anemia with excess blasts ).
4. All patients should aged 40 to 70 years
5. Have matched sibling donor.
6. Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases .

Exclusion Criteria

1. Patients aged less than 40 years old ;
2. Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases;
3. AML patients with t (15;17);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATG combined regimen	ATG	ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
ATG combined regimen	CsA	ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
ATG combined regimen	mycophenolate mofetil	ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
ATG combined regimen	Methotrexate	ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
no-ATG	CsA	regimen for prophylaxis of GVHD without ATG. The regimen includes MMF,CsA and MTX.CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
no-ATG	mycophenolate mofetil	regimen for prophylaxis of GVHD without ATG. The regimen includes MMF,CsA and MTX.CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.
no-ATG	Methotrexate	regimen for prophylaxis of GVHD without ATG. The regimen includes MMF,CsA and MTX.CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.

Primary Outcome Measures

Name	Time	Method
Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)	three years	Chronic graft versus host disease grading criteria (refer to NIH criteria)

Secondary Outcome Measures

Name	Time	Method
all cause mortality	two years
Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria	two years
DFS(disease-free survival )	two years	disease-free survival
TRM(treatment-related mortality )	two years	treatment-related mortality
Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)	three months

Trial Locations

Locations (1)

Liping Dou; 🇨🇳 Beijing, Beijing, China