Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04932564
Other study ID # 900643
Secondary ID CTRI/2021/04/033
Status Recruiting
Phase Phase 2
First received
Last updated
Start date June 15, 2021
Est. completion date April 9, 2023

Study information

Verified date June 2021
Source Tata Memorial Centre
Contact Sachin Punatar, MD, DM
Phone 02227405000
Email drsachin_punatar@yahoo.in
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

The curative potential of allogeneic hematopoietic stem cell transplantation (allo-HCT) is hampered by acute and chronic graft-versus-host disease (GVHD). Although chronic GVHD (cGVHD) can affect any organ / system in the body, commonly affected are skin, oral cavity, eyes, liver, joints and fascia, and lungs. Involvement of these can occur alone or concurrently, and these lead to a significant negative impact on the patient's quality of life. Musculoskeletal involvement in chronic GVHD (mGVHD) can have varied presentations like fasciitis, myositis, arthritis, etc. The basic pathogenesis of mGvHD closely mimics autoimmune disorders like rheumatoid arthritis, systemic sclerosis, systemic lupus, etc. The treatment goals of mGvHD include improvement or stabilisation of manifestations, limitation of long-term treatment related toxicities, improvement in functional capacity and quality of life. Corticosteroids, the standard frontline treatment, are typically administered for a median of 2 to 3years, leading to substantial morbidity. An effort to decrease corticosteroid doses has led to their use in combination with other drugs, such as cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, rituximab, etanercept, ruxolotinib, imatinib, ibrutinib, ECP (extra corporeal photopheresis), methotrexate etc, in frontline or second-line settings. All these drugs have been used with far and few responses but with significant treatment related toxicity and costs. As far as musculoskeletal GVHD is concerned, the British guidelines recommend corticosteroids as first line treatment and rituximab as second line option. However, the morbidity associated with long term steroid use warrants a quest for use of non-steroid therapies to be used in 1st line setting for chronic GVHD. Leflunomide has been used in rheumatoid arthritis. At our centre, the investigator have previously used leflunomide for patients with musculoskeletal GVHD and found it to be effective and safe. Leflunomide is relatively cheap and potentially more effective compared to other more expensive alternatives. If proven to be effective in a larger cohort of patients, this drug could become the standard first line agent in this setting. With this, the investigator have planned to carry out this study to assess the efficacy of leflunomide in musculoskeletal GVHD post allogeneic stem cell transplant.


Recruitment information / eligibility

Status Recruiting
Enrollment 10
Est. completion date April 9, 2023
Est. primary completion date April 9, 2023
Accepts healthy volunteers No
Gender All
Age group N/A to 65 Years
Eligibility Inclusion Criteria: 1. Willing to give written informed consent 2. Patients diagnosed with musculoskeletal mGvHD based on 2014 NIH consensus criteria (with diagnosis confirmed by biopsy only if clinically required). 3. Willing and able to comply with all study requirements, including treatment, and periodic assessments. Exclusion Criteria: 1. Patients with known hypersensitivity to leflunomide especially previous Steven Johnson syndrome, toxic epidermal necrolysis after leflunomide. 2. Pregnant females 3. Patients with musculoskeletal manifestations explained by other potential causes ( (drugs, trauma, etc). 4. Patients with calculated glomerular filtration rate (GFR) <30ml/min at the time of screening.

Study Design


Intervention

Drug:
Leflunomide tablet
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: <20 kg - 100 mg x 1 day followed by 10 mg every alternate day 20-40 kg - 100 mg x 2 days, followed by 10 mg daily >40 kg - Usual adult dose. This is scheduled to be continued for 1 year from the time of attaining complete response of musculoskeletal GVHD.

Locations

Country Name City State
India Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer Navi Mumbai Maharashtra

Sponsors (1)

Lead Sponsor Collaborator
Tata Memorial Centre

Country where clinical trial is conducted

India, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Time to response The time required to achieve complete or partial response after treatment. From date of start of leflunomide to date of first documented response, assessed up to 2 Years
Secondary Time to best response Time to best response will be recorded. From date of start of leflunomide to date of documented best response, assessed up to 2 Years
Secondary Duration of response The duration of response will be calculated from the time of onset of objective response after initiation of treatment with leflunomide until the end of the follow-up, GVHD relapse, the development of new or the deterioration of pre-existing mGVHD symptoms, or the reinstitution of any additional agents to control the disease. From date of first documented response to date of first documented progression or relapse, assessed up to 2 years
Secondary Relapse rate Relapse rate of mGVHD after stopping leflunomide will be recorded. Through study completion, an average of 2 years
See also
  Status Clinical Trial Phase
Completed NCT03042676 - Electronic Database for the Follow up of the ATG_FamilyStudy
Recruiting NCT05401955 - Physiotherapy and Therapeutic Exercise Program in Graft-versus-host Disease (GvHD) N/A
Not yet recruiting NCT06279676 - Improvement of Women's Health After Allogeneic Stem Cell Transplantation
Not yet recruiting NCT06169722 - TDI01 Suspension in the Treatment of Chronic Graft-versus-host Disease (cGVHD)) Phase 1/Phase 2
Terminated NCT04107675 - A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4) Phase 2
Recruiting NCT06462365 - Prevention of GvHD in Participants With Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplant (HSCT) Phase 1
Completed NCT04884204 - Systematic Symptom Identification With Disease Specific PROM to Assess Symptoms of Chronic GVHD in Outpatient Care in Patients Post HSCT N/A
Completed NCT04930562 - Efficacy and Safety of BN101 in Subjects With Chronic Graft Versus Host Disease (cGVHD) Phase 2