Leflunomide for Musculoskeletal GVHD After Allogeneic Stem Cell Transplant

NCT04932564 | Terminated Phase 2 DMC

• 2 other identifiers: 900643CTRI/2021/04/033214
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Graft versus host disease (GVHD) is a well-known complication of allogeneic transplant. In GVHD, the cells of the donor attack the patient's tissues and cause damage. It can affect any organ or system of the body. In a proportion of patients, it affects the joints and muscles. This is known as musculoskeletal GVHD. The standard treatment of musculoskeletal GVHD is steroids. However, these are usually needed for prolonged periods, and cause a large number of additional problems in transplant patients. Leflunomide is a drug which has been used for several years in diseases like rheumatoid arthritis (RA). RA is an auto-immune disorder. The biological mechanisms underlying RA and musculoskeletal GVHD are quite similar. Hence it is likely that leflunomide may work in musculoskeletal GVHD also. The investigator have previously used leflunomide in a few patients with musculoskeletal GVHD and have found it to be extremely effective. Also, it was very safe (unlike steroids). Yet another advantage is that it is fairly cheap. The purpose of the current study is to study the efficacy and safety of leflunomide in patients with musculoskeletal GVHD in a prospective way.

Conditions

Musculoskeletal Disease Other; GVHD, Chronic

Keywords

Musculosceletal GVHD; Leflunomide; Allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Overall objective response rate

  Response will be defined as per the NIH 2014 consensus response criteria working group for mGvHD.

  Through study completion, an average of 2 years

Secondary Outcomes (4)

• Time to response

  From date of start of leflunomide to date of first documented response, assessed up to 2 Years

• Time to best response

  From date of start of leflunomide to date of documented best response, assessed up to 2 Years

• Duration of response

  From date of first documented response to date of first documented progression or relapse, assessed up to 2 years

• Relapse rate

  Through study completion, an average of 2 years

Study Arms (1)

Leflunomide Arm

EXPERIMENTAL

Leflunomide will be given at standard dose (100 mg OD x 3 days followed by 20 mg OD) in adults and weight based dose in children. This is scheduled to be continued for 1 year from the time of attaining complete response of musculoskeletal GVHD.

Drug: Leflunomide tablet

Interventions

Leflunomide tablet DRUG

Leflunomide will be given at standard dose (100 mg OD x 3 days followed by 20 mg OD) in adults and weight based dose in children. The dosing for children will be as follows: 1. \<20 kg - 100 mg x 1 day followed by 10 mg every alternate day 2. 20-40 kg - 100 mg x 2 days, followed by 10 mg daily 3. \>40 kg - Usual adult dose. This is scheduled to be continued for 1 year from the time of attaining complete response of musculoskeletal GVHD.

Also known as: Leflunomide

Leflunomide Arm

Eligibility Criteria

• Age: 0 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to give written informed consent
• Patients diagnosed with musculoskeletal mGvHD based on 2014 NIH consensus criteria (with diagnosis confirmed by biopsy only if clinically required).
• Willing and able to comply with all study requirements, including treatment, and periodic assessments.

You may not qualify if:

• Patients with known hypersensitivity to leflunomide especially previous Steven Johnson syndrome, toxic epidermal necrolysis after leflunomide.
• Pregnant females
• Patients with musculoskeletal manifestations explained by other potential causes ( (drugs, trauma, etc).
• Patients with calculated glomerular filtration rate (GFR) \<30ml/min at the time of screening.

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (1)

Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer

Navi Mumbai, Maharashtra, 410210, India

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Leflunomide

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sachin Punatar, MD, DM

  Tata Memorial Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 5, 2021
• First Posted: June 21, 2021
• Study Start: September 18, 2023
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: September 10, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)