Mesenchymal Stem Cells (MSCs) for Steroid Refractory Acute GVHD (SR-aGVHD)
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 2M cells/kg 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
Direct IV infusion of OSSM-001
|
| Experimental: 6M cells/kg 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
Direct IV infusion of OSSM-001
|
| Experimental: 12M cells/kg 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
Direct IV infusion of OSSM-001
|
| Experimental: 24M cells/kg 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
Direct IV infusion of OSSM-001
|
Outcome Measures
Primary Outcome Measures
- Safety events [112 days (16 weeks)]
OSSM-001 related safety events
Secondary Outcome Measures
- Maximum tolerated dose (MTD) [112 days (16 weeks)]
Determine MTD of OSSM-001
Other Outcome Measures
- Overall survival (OS) from initiation of therapy [112 days (16 weeks)]
OS rate at day 112 post initiation of therapy
- Overall survival (OS) by baseline GVHD grading [112 days (16 weeks)]
OS rate at day 112 by baseline GVHD grading post initiation of therapy
- Overall survival (OS) stratified by organ involvement [112 days (16 weeks)]
OS rate at day 112 stratified by organ involvement post initiation of therapy
- Overall disease relapse [112 days (16 weeks)]
Overall disease relapse by day 112 post initiation of therapy
- Overall opportunistic infection rate [112 days (16 weeks)]
Overall opportunistic infection rate by day 112 post initiation of therapy
Eligibility Criteria
Criteria
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:
- Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day), OR
- 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.
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Patients who have received more than one HCT
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Any medical or psychological condition or situation deemed by the Investigators to put the patient at increased risk of complications or non-compliance.
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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)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Ossium Health, Inc.
Investigators
- Study Director: Sagar Munjal, Ossium Health, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OSSM-001-006-01