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

• 180 day mortality, acute Graft versus Host Disease (GvHD) grades III-IV, engraftment failure [ Time Frame: 180 days ]
• Safety and tolerability measures: The incidence and frequency of adverse experiences, acute toxicity, laboratory data and vital signs follow-up. [ Time Frame: 180 days ]

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.

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:

1. Screening phase includes subjects' clinical assessment and screening tests
2. Conditioning phase includes the myeloablative treatment prior transplantation procedure
3. Transplantation and post-transplant follow-up phase to day 180
4. Observational phase: survival status follow-up to day 730 (18 months)

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

• Peled T, Landau E, Prus E, Treves AJ, Nagler A, Fibach E. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells. Br J Haematol. 2002 Mar;116(3):655-61. Erratum in: Br J Haematol 2002 May;117(2):485.
• Peled T, Landau E, Mandel J, Glukhman E, Goudsmid NR, Nagler A, Fibach E. Linear polyamine copper chelator tetraethylenepentamine augments long-term ex vivo expansion of cord blood-derived CD34+ cells and increases their engraftment potential in NOD/SCID mice. Exp Hematol. 2004 Jun;32(6):547-55.
• Prus E, Peled T, Fibach E. The effect of tetraethylenepentamine, a synthetic copper chelating polyamine, on expression of CD34 and CD38 antigens on normal and leukemic hematopoietic cells. Leuk Lymphoma. 2004 Mar;45(3):583-9.
• Peled T, Mandel J, Goudsmid RN, Landor C, Hasson N, Harati D, Austin M, Hasson A, Fibach E, Shpall EJ, Nagler A. Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. Cytotherapy. 2004;6(4):344-55.
• Peled T, Glukhman E, Hasson N, Adi S, Assor H, Yudin D, Landor C, Mandel J, Landau E, Prus E, Nagler A, Fibach E. Chelatable cellular copper modulates differentiation and self-renewal of cord blood-derived hematopoietic progenitor cells. Exp Hematol. 2005 Oct;33(10):1092-100.
• de Lima M, McMannis J, Gee A, Komanduri K, Couriel D, Andersson BS, Hosing C, Khouri I, Jones R, Champlin R, Karandish S, Sadeghi T, Peled T, Grynspan F, Daniely Y, Nagler A, Shpall EJ. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant. 2008 May;41(9):771-8. Epub 2008 Jan 21.

Inclusion Criteria:

1. 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.
2. 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.
3. Clinical diagnosis of HD: induction failure or relapse and sensitive to last chemotherapy course.
4. Clinical diagnosis of NHL induction failure or relapse and sensitive to last chemotherapy course.
5. Clinical diagnosis of MDS with intermediate 2- or high-risk IPSS score.

Exclusion Criteria:

1. Less than twenty-one days have elapsed since the subject's last radiation or chemotherapy prior to conditioning (except Hydroxyurea).
2. HIV positive.
3. Pregnancy or lactation.
4. Uncontrolled bacterial, fungal or viral infection.
5. Subjects with signs and symptoms of active central nervous system (CNS) disease.
6. Availability of appropriate related and willing stem cell donor, who is HLA-matched at 5 or 6/6 antigens.
7. Prior allogeneic cell transplant.
8. Allergy to bovine or to any product, which may interfere with the treatment.
9. Enrolled in another clinical trial or received an investigational treatment during the last 30 days, unless approved by Sponsor.