Pilot study of leflunomide as first line therapy for musculoskeletal GVHD
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Dr Sachin Punatar
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Overall objective response rate
Overview
Brief Summary
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, etanarcept, ruxulotinib, 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, we 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, we have planned to carry out this study to assess the efficacy of leflunomide in musculoskeletal GVHD post allogeneic stem cell transplant.
Study Design
- Study Type
- Interventional
- Allocation
- Not Applicable
- Masking
- Not Applicable
Eligibility Criteria
- Ages
- 0.00 Year(s) to 65.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •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.
Exclusion Criteria
- •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 GFR <30ml/min at the time of screening.
Outcomes
Primary Outcomes
Overall objective response rate
Time Frame: At any time following start of intervention
Secondary Outcomes
- Time to response(Time from start of leflunomide to attainment of any response)
- Time to best response(Time from start of leflunomide to the best response)
- Duration of response(Time from first response to relapse or progression of musculoskeletal GVHD)
- Relapse rate(Proportion of patients relapsing after attaining a response)