ExCell Information for Physicians

Background

According to the National Marrow Donor Program, each year in the U.S., more than 70% of the 35,000 patients with life-threatening diseases who could benefit from a bone marrow transplant, can not be matched with a donor. Research shows that cells derived from umbilical cord blood can effectively be used for bone marrow transplantation.

Cord blood grafts have lower matching requirements than bone marrow or peripheral blood grafts, providing the potential to increase the number of suitable transplant matches and shorten the time it takes to find a match. In addition, cord blood transplants have been associated with a reduced risk for Graft versus Host Disease (GvHD).

Umbilical cord blood contains a limited number of stem/progenitor cells and therefore has been used historically for transplants in small children, who require fewer numbers of these cells. StemEx® employs an innovative technology platform to increase the number of stem cells available in a single unit of cord blood, in order to allow transplantation in adolescents and adults. The preliminary results of the Phase I/II study of StemEx® presented at the 2004 Annual Meeting of the American Society of Hematology (ASH) in San Diego, encouraged the further investigation of the safety and efficacy of StemEx®, in the ExCell study.

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Description of StemEx®

Successful ex-vivo expansion of hematopoietic progenitor cells (HPC) depends on their ability to proliferate while maintaining their basic characteristics. While most protocols for ex-vivo expansion utilize various combinations of cytokines that support extensive proliferation of cultured cells, this process is tightly coupled with commitment and differentiation, thereby lessening the clinical utility of cultured cells. We have developed a proprietary technology for ex-vivo expansion of HPC utilizing a low molecular weight copper chelator, Tetraethylpentamine (TEPA). TEPA reduces intracellular copper levels, delays differentiation and enables robust and large-scale ex vivo expansion of stem/progenitor cells with limited differentiation, within a reasonably short time.

StemEx® is composed of stem/progenitor cells expanded ex-vivo from a portion of a single unit of umbilical cord blood and transplanted in combination with the remaining, non-expanded cells from the same unit.

1National Marrow Donor Program. "Facts and Figures."  Selected publications

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ExCell Study

The study's official title is "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".

ExCell is a single arm, multi-center study to assess the efficacy and safety of StemEx® transplantation as a treatment for hematological malignancies, i.e., leukemias and lymphomas. StemEx® transplantation will be compared to historical controls.

The FDA granted ExCell a Special Protocol Assessment (SPA) in October 2006. Therefore, the study results of the Phase II/III study may be used to support the registration of StemEx®.

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Study objectives

The primary objective of the ExCell study is to assess the effect of StemEx® transplantation on overall 100–day survival. Other objectives include assessment of 180 day overall survival, engraftment, and rate of Graft vs. Host Disease.

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Study design

Patients will undergo myeloablative conditioning. On day 0, the unmanipulated fraction of the cord blood unit will be transplanted. The expanded fraction of the unit will be transplanted after 24 hours.

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Eligible patients

Adolescents and adults (ages 12-55 years), with high-risk hematological malignancies, including acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), who are candidates for hematopoietic myeloablative stem cell transplantation from an unrelated donor, may be eligible for ExCell.  The study is currently enrolling 100 patients

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Eligibility for the Study

  1. 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. CML: in CP1 (Chronic Phase 1) and resistant or intolerant to Gleevec  or in CP2 or subsequent CP or in accelerated phase.
  3. HD: induction failure or relapse and sensitive to last chemotherapy course.
  4. NHL induction failure or relapse and sensitive to last chemotherapy course.
  5. MDS with intermediate 2- or high-risk IPSS score.

Further eligibility criteria will be determined by the investigator in accordance with the ExCell study protocol.

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