Mesenchymal Stem Cells (MSCs) for Steroid Refractory Acute GVHD (SR-aGVHD)

Study Overview
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Brief Summary
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The objective of this clinical study is to demonstrate safety and feasibility of single-dose infusion of Ossium MSCs product (OSSM-001) to treat steroid refractory acute GVHD (SR-aGVHD).

Detailed Description
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The dose escalation will be used to establish a maximum tolerated dose, starting from 2M cells/kg. If no safety issues are seen, then MSCs dose maybe escalated to 6M cells/kg, 12M cells/kg and 24M cell/kg based on data review from each cohort. Additional studies will be conducted to establish a dosing regimen and to evaluate the safety and efficacy of OSSM-001 for SR-aGVHD patients.

Official Title
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A Phase I Safety Study of Single Dose Allogeneic Bone Marrow Derived MSCs for Steroid Refractory Acute Graft vs. Host Disease

Conditions
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GVHD,Acute

Intervention / Treatment
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* Biological: OSSM-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum 18 years of age who have undergone hematopoietic cell transplantation (HCT), from any donor source donor (including HLA-matched related and unrelated, haploidentical and umbilical cord donors) with any conditioning regimen Clinically diagnosed Grades II to IV acute GVHD as per standard criteria occurring within 100 days of HCT Confirmed diagnosis of steroid refractory aGVHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either: Progressing based on organ assessment after at least 3 days at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGVHD, OR Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGVHD, OR Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria: i. Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day), OR ii. Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days. Minimum Karnofsky Performance Level of at least 30 or higher at the time of study entry. Exclusion Criteria: Has received more than one systemic treatment for steroid refractory aGVHD in addition to steroids. Received stem cell therapy in the past Presence of an active uncontrolled infection including significant bacterial, fungal, viral, or parasitic infection requiring treatment Presence of relapsed primary malignancy, or who have been treated for relapse after the HCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse. Evidence of pulmonary infiltrate or hemorrhage based on imaging or requiring high flow oxygen via face mask Patients who have had treatment with any other investigational agent, device, or procedure within 30days (or 5 half-lives, whichever is greater) prior to enrollment. Patients who have received more than one HCT Any medical or psychological condition or situation deemed by the Investigators to put the patient at increased risk of complications or non-compliance. Unresolved veno-occlusive disease HLA antibody screen positive for HLA antibodies specific against the MSCs products ALT or AST > 5X of upper limit of normal Serum Bilirubin >2 X of upper limit of normal GFR <50 ml/min SpO2 <94% despite being on continuous supplemental oxygen Patients requiring continuous >4L/minute of supplemental oxygen (irrespective of oxygen saturation)

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2M cells/kg<br>Dose level 1. 3 subjects will receive OSSM-001 at 2M cells/kg and followed for 28 days post dose to observe for DLT. | Biological: OSSM-001<br>* Direct IV infusion of OSSM-001<br>|
| Experimental: 6M cells/kg<br>Dose level 2. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 6M cells/kg and followed for 28 days post dose to observe for DLT. | Biological: OSSM-001<br>* Direct IV infusion of OSSM-001<br>|
| Experimental: 12M cells/kg<br>Dose level 3. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 12M cells/kg and followed for 28 days post dose to observe for DLT. | Biological: OSSM-001<br>* Direct IV infusion of OSSM-001<br>|
| Experimental: 24M cells/kg<br>Dose level 4. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 24M cells/kg and followed for 28 days post dose to observe for DLT. | Biological: OSSM-001<br>* Direct IV infusion of OSSM-001<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety events | OSSM-001 related safety events | 112 days (16 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Determine MTD of OSSM-001 | 112 days (16 weeks) |