Safety and Efficacy Study of Adult Human Mesenchymal Stem Cells to Treat Acute Graft Versus Host Disease (GVHD)

Study Overview
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Brief Summary
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To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant.

Detailed Description
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Protocol 260 - Participants will be randomized with equal probability to the treatment arms (2 million cells/kilogram (kg) of Prochymal® or 8 million cells/kg of Prochymal®) using a stratified block design. The stratification factor is acute GVHD grade. For the purpose of stratification, the GVHD grades are II and III-IV. Treatment with investigational agent will be administered on study Days 1 and 4. Participants will be followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurs first. Protocol 261- This study is designed as a long-term safety follow-up of participants who take part in the preceding clinical study of Prochymal® (Protocol 260) for the treatment of acute GVHD. Participants will be enrolled in Study 261 upon completion of the preceding Study 260.

Official Title
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A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) For the Treatment of Acute GVHD in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Graft Vs Host Disease

Intervention / Treatment
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* Drug: Prochymal® - 2 Million cells/kg
* Drug: Prochymal®- 8 Million cells/kg
* Drug: Methylprednisolone
* Drug: Prednisone
* Drug: Cyclosporine
* Drug: Tacrolimus
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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Protocol 260 Inclusion Criteria: Participant must be 18 to 70 years of age inclusive. If female and of child-bearing age, participant must be non-pregnant, not breast feeding, and use adequate contraception. Males must use adequate contraception. Participant must have newly diagnosed, Grade II-IV acute GVHD requiring therapy. Biopsy for confirmation of GVHD is not mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting biopsy results. Participant must have received either full or reduced intensity myeloablative regimens followed by an allogeneic hematopoietic stem cell transplant using bone marrow, peripheral blood stem cell, or cord blood, including donor lymphocyte infusion (DLI). Participant must have minimal renal and hepatic function as defined by: * Calculated creatinine clearance (CLcr) of > 30 mL/min using the Cockroft-Gault equation. Participant must be available for all specified assessments at the study site through study Day 28. Participant must provide written informed consent and authorization for use and disclosure of protected health information (PHI). Protocol 260 Exclusion Criteria: Participant has received previous treatment for Grade II-IV acute GVHD (except as noted in Criterion 2). Participant has been treated for GVHD with methylprednisolone, > 2mg/kg/day, for more than 72 hours prior to receiving Prochymal®. Participant has uncontrolled alcohol or substance abuse within 6 months of randomization. Participant has received an investigational agent (not approved by food and drug administration (FDA) for marketed use in any indication) within 30 days of randomization. Participant may not receive an investigational agent during the 28-day study period. 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 unstable arrhythmia. Participant is unwilling to sign consent form for the long-term follow-up study, Protocol 261. Participant has a known allergy to bovine or porcine products. Participant had received transplant for a solid tumor disease.

Ages Eligible for Study
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Minimum Age: 18 Years
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prochymal® - 2 Million cells/kg<br>Participants will receive Prochymal® consisting of 2 million hMSCs/kg actual body weight, intravenously (IV) on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 milligrams (mg)/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. | Drug: Prochymal® - 2 Million cells/kg<br>* 2 million hMSCs/kg actual body weight, IV on study Days 1 and 4<br>* Other names: hMSCs;Drug: Methylprednisolone<br>* Methylprednisolone 2 mg/kg administered intravenously.<br>Drug: Prednisone<br>* Prednisone 2.5 mg/kg administered orally.<br>Drug: Cyclosporine<br>* Administered as prescribed by the caregiver.<br>Drug: Tacrolimus<br>* Administered as prescribed by the caregiver.<br>Drug: Mycophenolate Mofetil<br>* Administered as prescribed by the caregiver.<br>|
| Active Comparator: Prochymal® - 8 Million cells/kg<br>Participants will receive Prochymal® consisting of 8 million hMSCs/kg actual body weight IV on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 mg/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. | Drug: Prochymal®- 8 Million cells/kg<br>* 8 million hMSCs/kg actual body weight IV on study Days 1 and 4<br>* Other names: hMSCs;Drug: Methylprednisolone<br>* Methylprednisolone 2 mg/kg administered intravenously.<br>Drug: Prednisone<br>* Prednisone 2.5 mg/kg administered orally.<br>Drug: Cyclosporine<br>* Administered as prescribed by the caregiver.<br>Drug: Tacrolimus<br>* Administered as prescribed by the caregiver.<br>Drug: Mycophenolate Mofetil<br>* Administered as prescribed by the caregiver.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR) |  | 28 Days | 
| Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260). |  | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1, |  | 28 Days | 
| Protocol 260 - Time to best response of GVHD |  | 28 Days | 
| Protocol 260 - Time to improvement of GVHD in one or more organs |  | 28 Days | 
| Protocol 261 - Survival through study day 90 |  | 90 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft vs Host Disease, (GVHD), Graft Versus Host Disease, Bone marrow transplant, Stem cells, Mesenchymal stem cells (MSCs), Adult stem cells, Leukemia, Lymphoma