Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of transplanting StemEx® in patients with certain hematological malignancies. For these patients, it is suggested that StemEx® can improve upon the outcome of transplanting a single, unmanipulated cord blood unit by significantly increasing the number of stem/progenitor cells available to the patient.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for patients with hematologic malignancies; yet wide application of this procedure is limited by the availability of suitably Human Leukocyte Antigen (HLA) - matched donors. Only 30% of patients who could benefit from this procedure have an HLA-matched sibling. The lengthy search for a matched donor may critically delay transplantation. In addition, far fewer patients of racial minorities find suitable HLA-matched donors. Umbilical cord blood (UCB) has been increasingly used as an alternative source of stem cells; however, its use in adults and adolescent patients is limited due to insufficient cell dose required for satisfactory hematopoietic reconstitution. Gamida Cell - Teva Joint Venture Ltd. is engaged in the development of StemEx®, an expanded hematopoietic UCB stem cell graft, as a potential medicinal product for the treatment of cancer and hematological malignancies. The expansion technology enables preferential expansion of hematopoietic stem and early progenitor cells and is based on the findings that copper chelators can regulate the balance between self-renewal and differentiation of stem cells. The multi-national, multi-center Phase II/III clinical study designated to evaluate the safety and efficacy of StemEx® will enroll approximately 100 subjects with high-risk hematologic malignancies who are candidates for allogeneic stem cell transplantation (SCT). This study will evaluate the effect of StemEx® on overall survival as measured by overall 100-day mortality. The study consists of 4 phases: Screening phase includes subjects' clinical assessment and screening tests Conditioning phase includes the myeloablative treatment prior transplantation procedure Transplantation and post-transplant follow-up phase to day 180 Observational phase: survival status follow-up to day 730 (18 months)

Official Title
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A Multi-Center, Multi-National, Historical Cohort Controlled Study to Evaluate Efficacy and Safety of Transplantation of StemEx®, Umbilical Cord Blood Stem and Progenitor Cells Expanded Ex Vivo, in Subjects With Hematologic Malignancies Following Myeloablative Therapy

Conditions
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Hematologic Malignancies, Acute Myeloid Leukemia, Lymphoid Leukemia, Chronic Myeloid Leukemia, Hodgkin's Disease, Non-Hodgkin's Lymphoma, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: StemEx®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of AML or ALL: CR2 or subsequent complete remission (CR) or CR1 with high-risk features or relapse with < 10% blasts in BM and no circulating blasts. Clinical diagnosis of CML: in CP1 (Chronic Phase 1) and resistant or intolerant to Gleevec or in CP2 or subsequent CP or in accelerated phase. Clinical diagnosis of HD: induction failure or relapse and sensitive to last chemotherapy course. Clinical diagnosis of NHL induction failure or relapse and sensitive to last chemotherapy course. Clinical diagnosis of MDS with intermediate 2- or high-risk IPSS score. Exclusion Criteria: Less than twenty-one days have elapsed since the subject's last radiation or chemotherapy prior to conditioning (except Hydroxyurea). HIV positive. Pregnancy or lactation. Uncontrolled bacterial, fungal or viral infection. Subjects with signs and symptoms of active central nervous system (CNS) disease. Availability of appropriate related and willing stem cell donor, who is HLA-matched at 5 or 6/6 antigens. Prior allogeneic cell transplant. Allergy to bovine or to any product, which may interfere with the treatment. Enrolled in another clinical trial or received an investigational treatment during the last 30 days, unless approved by Sponsor.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 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: StemEx<br> | Drug: StemEx®<br>* The stem/progenitor cell based product composed of ex vivo expanded allogeneic umbilical cord blood cells, which is infused to subject at a rate of 1-3 ml/min in combination with non-manipulated cells derived from the same cord blood unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall 100-day mortality |  | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 180 day mortality, acute Graft versus Host Disease (GvHD) grades III-IV, engraftment failure |  | 180 days | 
| Safety and tolerability measures: The incidence and frequency of adverse experiences, acute toxicity, laboratory data and vital signs follow-up. |  | 180 days | 
| Proportion of overall mortality at 1 year |  | One year post transplant | 
| Proportion of overall mortality at 2 years |  | Two years post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tetraethylenepentamine, Umbilical Cord Blood Stem Cell Transplantation, Hematological Malignancies, Acute Lymphoid Leukemia, Subjects with high-risk hematologic malignancies who are candidates for allogeneic stem cell transplantation