Musculoskeletal Disease OtherPhase 2NCT04932564
Leflunomide for Musculoskeletal GVHD After Allogeneic Stem Cell Transplant
A Phase 2 study testing Leflunomide tablet in people with Musculoskeletal Disease Other and GVHD, Chronic, run by Tata Memorial Centre at 1 site in India.
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. Read more about this study
- Who is it for?
- Ages 0 to 65 years
- Conditions the study is for
- Musculoskeletal Disease Other, GVHD, Chronic
- What is being tested?
- Leflunomide tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteIndia
- Study dates
- 18 Sep 2023to 25 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
India1 site
Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer
Navi Mumbai, Maharashtra, 410210
About this study
Official title: Pilot Study of Leflunomide as First Line Therapy for Musculoskeletal GVHD
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.
Read the detailed 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.
- Conditions
- Musculoskeletal Disease Other, GVHD, Chronic
- Being tested
- Leflunomide tablet
- Keywords
- Musculosceletal GVHD, Leflunomide, Allogeneic stem cell transplant
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leflunomide tabletDrug
Also called Leflunomide
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Leflunomide tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall objective response rate
Response will be defined as per the NIH 2014 consensus response criteria working group for mGvHD.
Measured: Through study completion, an average of 2 years
Secondary outcomes (4)
Time to response
The time required to achieve complete or partial response after treatment.
Measured: From date of start of leflunomide to date of first documented response, assessed up to 2 Years
Time to best response
Time to best response will be recorded.
Measured: From date of start of leflunomide to date of documented best response, assessed up to 2 Years
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.
Measured: From date of first documented response to date of first documented progression or relapse, assessed up to 2 years
Relapse rate
Relapse rate of mGVHD after stopping leflunomide will be recorded.
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2021
- Study start18 Sep 2023
- Primary completion25 Jun 2024
- Study completion25 Jun 2024
Why it stopped: Issues with recruitment. Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Musculoskeletal Disease OtherStudies of the same condition, open and under way.
- More trials run by Tata Memorial CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Sachin Punatar, Tata Memorial Centre
- Investigators
- Sachin Punatar, MD, DM, Principal investigator, Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04932564
- Sponsor's protocol ID
- 900643
- Other IDs
- CTRI/2021/04/033214
- Status last verified
- Apr 2024
- First submitted
- 5 Jun 2021
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Leflunomide as First Line Therapy for Musculoskeletal GVHD
- ClinicalTrials.gov ID
- NCT04932564
- Acronym / sponsor ID
- 900643
- Conditions
- Musculoskeletal Disease Other, GVHD, Chronic
- Keywords
- Musculosceletal GVHD, Leflunomide, Allogeneic stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Issues with recruitment. Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Tata Memorial CentreUniversity, hospital or other
- Study start
- 18 Sep 2023 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 25 Jun 2024 (actual)
- First posted
- 21 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Leflunomide Arm | Experimental | Drug: Leflunomide tabletLeflunomide 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. |
Who may qualify
- Ages
- 0 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leflunomide tabletAlso: LeflunomideLeflunomide 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. | Drug | Leflunomide Arm |
Primary outcome
Overall objective response rate
Time frame: Through study completion, an average of 2 years
Response will be defined as per the NIH 2014 consensus response criteria working group for mGvHD.
4 secondary outcomes
Time to response
Time frame: From date of start of leflunomide to date of first documented response, assessed up to 2 Years
Time to best response
Time frame: From date of start of leflunomide to date of documented best response, assessed up to 2 Years
Duration of response
Time frame: From date of first documented response to date of first documented progression or relapse, assessed up to 2 years
Relapse rate
Time frame: Through study completion, an average of 2 years
Results and safety
The study was stopped early (reason given: Issues with recruitment. Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sachin Punatar, MD, DM principal investigator
Tata Memorial Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leflunomide tablet in people with Musculoskeletal Disease Other and GVHD, Chronic, run by Tata Memorial Centre at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Issues with recruitment. Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall objective response rate (time frame: Through study completion, an average of 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.