Safety and Efficacy of Prochymal® for the Salvage of Treatment-Refractory Acute GVHD Patients

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and efficacy of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) in participants experiencing treatment-refractory acute GVHD, Grades III-IV, that is refractory to standard first-line therapies and at least one second-line therapy.

Detailed Description
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Allogeneic hematopoetic stem cell transplantation (HCT) is used in the treatment of a variety of hematological, myeloproliferative and lymphoproliferative disorders, and malignancies involving solid tumors. Patients receiving HCT can develop a life-threatening condition called graft versus host disease (GVHD). GVHD occurs when donor T cells from the donor bone marrow recognize host cells as foreign and initiate an inflammatory immunological response. The standard of care for treatment of acute GVHD consists of intravenous delivery of methylprednisolone starting on day 1 and continuation of either cyclosporine or tacrolimus. This regimen of steroids and immunosuppressive drugs may relieve symptoms of GVHD, but some patients are refractory to current standard of care treatment. For treatment-refractory patients with grades III-IV GVHD mortality is approximately 80%. A therapy that could effectively suppress the immunological response from GVHD and help repair the damaged tissue could significantly decrease the mortality rate from this disease.

Official Title
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A Phase II Open Label Study to Evaluate the Safety and Efficacy of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion for the Salvage of Treatment-Refractory Acute GVHD Patients

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Drug: Prochymal®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 6 months to 70 years of age inclusive. If female and of childbearing age, participants must be non-pregnant, not breast-feeding, and use adequate contraception. Male participants must use adequate contraception. Participants must have Grade III-IV acute GVHD that has failed to respond to standard first and at least one second-line therapy. Biopsy for confirmation of both skin and gastrointestinal GVHD is not mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting biopsy results. Participants must have minimal renal function as defined by: Calculated creatinine clearance (CrCl) of > 30 milliliters/minute (mL/min) using the Cockcroft-Gault equation. Participants must provide written informed consent and authorization for use and disclosure of protected health information (PHI). Exclusion Criteria: Participant has uncontrolled alcohol or substance abuse within 6 months of treatment. Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant (e.g., uncontrolled infection, right heart failure, pulmonary hypertension, etc.). Participant has a clinically significant, unstable arrhythmia. Participant has a known allergy to bovine or porcine products. Participant is unwilling to sign consent form for the long-term follow-up study, Protocol 271.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prochymal®<br> | Drug: Prochymal®<br>* Intravenous infusion of ex-vivo cultured adult human mesenchymal stem cells<br>* Other names: Remestemcel-L;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response by Day 28 |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at day 1 |  | Day 1 | 
| Best stage of each involved organ by Day 28 |  | Day 28 | 
| Time to improvement or resolution of GVHD in one or more organs |  | Up to approximately 12 months | 
| Adverse events |  | Up to approximately 12 months | 
| Infusional toxicity |  | Up to approximately 12 months | 
| Overall relapse of underlying disease |  | Up to approximately 12 months | 
| Overall survival |  | Up to approximately 12 months | 
| Formation of ectopic tissue foci |  | Up to approximately 12 months | 
| Incidence of infection |  | Up to approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GVHD, Graft vs Host Disease, Graft versus Host Disease