MTX and Steroid for III-IV aGVHD Treatment

A Single-cohort, Phase II Study of Methotrexate Combined Corticosteroid in Chinese Patients With Grade III-IV Acute Graft vs. Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

The aim of the study is to identify the efficacy and safety of methotrexate (MTX) combined corticosteroid treatment for grade III-IV acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Study Overview

• Status: Recruiting
• Conditions: Acute Graft Versus Host Disease
• Intervention / Treatment: Drug: Methotrexate

Detailed Description

Allo-HSCT is an effective treatment of malignant hematopoietic diseases. However, aGVHD remains a major complication after allo-HSCT and the destruction of recipient tissues by alloantigen-activated T cells is a key event in the development of aGVHD. Corticosteroid is the standard first-line therapy for aGVHD due to their roles in suppressing T cell responses. However, the response rate of corticosteroid was approximate 50%, and the clinical outcomes of patients with corticosteroid refractory GVHD were poor. Thus far, no combination therapy had been prove to be superior to corticosteroid alone as initial therapy for aGVHD. The study hypothesis: MTX combined corticosteroid treatment could help to further ameliorate the activity of T cells and control aGVHD.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Wang, Dr.; Phone Number: 86-13552647384; Email: ywyw3172@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Institute of Hematology,
      • Contact: Yu Wang, Dr.; Phone Number: 13552647384; Email: ywyw3172@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who are fully informed and sign informed consent by themselves or their guardians;
2. Patients receiving allogeneic hematopoietic stem cell transplantation;
3. Patients with acute graft-versus-host disease of grade III-IV were diagnosed after transplantation;
4. Patients with stable implantation of granulocytes and platelets.

Exclusion Criteria:

1. Patients who have received more than one transplant;
2. Patients with overlap syndrome;
3. Patients within six months after the failure of the first transplantation;
4. Patients with uncontrollable active infection;
5. Patients with recurrence of primary malignant hematopathy;
6. Patients with donor lymphocyte infusion induced graft-versus-host disease after first intervention;
7. Patients with serious respiratory diseases;
8. Patients with severe renal insufficiency;
9. Patients with serious and uncontrolled heart disease;
10. Patients with severe hepatobiliary diseases unrelated to graft-versus host disease;
11. Within one week patients who need to use more than 1mg/kg/d methylprednisolone for reasons other than graft-versus-host disease;
12. patients who have participated in other clinical trials within 1 month;
13. The researcher judges that there are other factors that are not suitable for participating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: MTX and corticosteroid; Methylprednisolone 2 mg/kg/day MTX (5-10 mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II	Drug: Methotrexate; Methylprednisolone 2 mg/kg/day MTX (5-10 mg/day) was given on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II; Other Names: Corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) for GVHD treatment after treatment	Overall response rate is defined as the proportion of patients demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	1 year
Non-relapse mortality	Non-relapse mortality	1 year
Disease free survival	Disease free survival	1 year
Failure free survival	Failure free survival	1 year
Overall response rate (ORR) at 28 days after treatment	Overall response rate is defined as the proportion of patients demonstrating a complete response or partial response without requirement for additional systemic therapies for an earlier progression, mixed response or non-response	28 days
relapse rate	Relapse rate is defined as the proportion of patients demonstrating a morphological relapse of the original malignant hematological disease	1 year
Chronic GVHD	number of participants with chronic GVHD at one year	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety data (side effect)	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.Data collection including questionnaires at individual and group visits and physician interviews at individual visits will be used to assess participants for treatment-related adverse events.	1 year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiao-Jun Huang, Dr., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): January 30, 2023

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Corticosteroid; MTX; acute GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: GVHD-MTX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No