Abatacept s.c. for aGVHD Prevention in Haplo-HCT

The Efficacy and Safety of Subcutaneous Abatacept in the Prevention of Acute Graft-versus-host Disease After Haplo-identical Donor Hematopoietic Cell Transplantation

Acute graft-versus-host disease (aGVHD) is a potentially fatal complication after allogeneic hematopoietic cell transplantation (HCT), particularly for that with a HLA-mismatched donor. Abatacept has been demonstrated as a potent drug to reduce the risk of aGVHD, but the efficacy of subcutaneous form has yet been investigated. This trial is designed to preliminarily determin the efficacy and saftey of subcutaneous abatacept in the prevention of aGVHD after haplo-identical HCT.

Study Overview

• Status: Recruiting
• Conditions: Prevention; Acute-graft-versus-host Disease; Abatacept; Haplo-identical HCT
• Intervention / Treatment: Drug: Abatacept s.c.

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jia Chen, M.D.; Phone Number: +86 512 6778 1856; Email: drchenjia@163.com
• Study Contact Backup: Name: Xiang Zhang; Phone Number: +86 512 6778 1850; Email: lcsy2013@sina.com.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age≧18 years
2. ECOG score 0-2 / Karnofsky score≧80
3. haplo-HCT is proposed
4. Conditioning with motified Bu/Cy+ATG regimen

5. Having the following hematologic malignancies with transplant indications:

   1. Acute leukemia
   2. Myelodysplastic syndrome
   3. Aggressive lymphoma
6. Expected survival ≥ 3 months
7. Written informed Consent can be acquired
8. Agree to use effective contraception

Exclusion Criteria:

1. With a history of allo-HCT previously
2. Allergic/intolerant to Abatacept
3. Contraindications to the use of Abatacept
4. HIV infection, or active HBV infection or HCV infection
5. Uncontrolled active infection
6. Vital organ function intolerated to transplantation
7. Other malignancies except for the following diseases: malignant tumors that have been cured for at least 3 years without active lesions; adequete treated non-melanoma skin cancer, malignant amygdala, and carcinoma in situ without active lesions
8. Evidence of complications or medical conditions that may interfere with research or put the subjects at serious risk, including but not limited to severe cardiovascular disease (e.g. New York Heart Association grade III or IV heart disease, myocardial infarction in the past 6 months, unstable arrhythmia or unstable angina) and/or severe lung disease (e.g. history of severe obstructive lung disease and symptomatic bronchospasm)
9. Pregnant and lactational women
10. Any life-threatening disease, medical condition, or organ dysfunction unfit for participants, or may interfere with the absorption or metabolism of Abatacept

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; The participants in Cohort 1 will receive abatacept s.c	Drug: Abatacept s.c.; subcutaneous abatacept: 250mg (d-1) , 125mg (d+5, +14, +21, +28, +35, +42, +49, +56) combined with CsA, MTX, MMF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of overt aGVHD	The incidence of grade II-IV aGVHD post-transplantation	100 days post-HCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of aGVHD	The incidence of grade I-IV aGVHD post-transplantation	100 days post-HCT
Incidence of severe aGVHD	The incidence of grade III-IV aGVHD post-transplantation	100 days post-HCT
Early transplant-related mortality	The incidence of early transplant-related mortality	100 days post-HCT
Relapse	The incidence of relapse/progression of underlying disease	100 days post-HCT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraft failure	Failed to engraft with donor cells	100 days post-HCT
Blood cell recovery	Neutrophil count recover to 1000/ul and platelet count recover to 20000/ul	100 days post-HCT

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: SZ9102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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