Clinical trial NCT00469729: Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hematologic Malignancies
Acute Myeloid Leukemia
Lymphoid Leukemia
Chronic Myeloid Leukemia
Hodgkin's Disease
Non-Hodgkin's Lymphoma
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Gamida Cell -Teva Joint Venture Ltd.
Sponsor class: OTHER
First posted: 2007-05-04
Enrollment: 101
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Overall 100-day mortality
timeFrame: 100 days
Secondary outcomes:
measure: 180 day mortality, acute Graft versus Host Disease (GvHD) grades III-IV, engraftment failure
timeFrame: 180 days
measure: Safety and tolerability measures: The incidence and frequency of adverse experiences, acute toxicity, laboratory data and vital signs follow-up.
timeFrame: 180 days
measure: Proportion of overall mortality at 1 year
timeFrame: One year post transplant
measure: Proportion of overall mortality at 2 years
timeFrame: Two years post transplant
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA's Jonsson Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: The Children's Hospital, B115, University of Colorado Health Sciences Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine
state: Illinois
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Cornell University, Joan & Sanford I. Weill Medical College
state: New York
city: New York
country: United States
facility: Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: One Gustave L Levy Place, BOX 1410, New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: The Western Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute/UPMC Cancer Centers
state: Pennsylvania
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: West Complex 1300 Jefferson Park Av, Charlottesville
country: United States
facility: University of Virginia, Hematopoietic Stem Cell Transplant Program
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Division of Neoplastic Diseases and Related Disorders
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Pediatric Blood and Marrow Transplant Program
state: Wisconsin
city: Budapest
country: Hungary
facility: Szent Laszlo & Szent Istvan Hospital
city: Jerusalem
country: Israel
facility: Hebrew University Hospital Ein-Karem, Department of Bone Marrow Transplantation And Cancer Immunotherapy
city: PO Box 9602, Haifa
country: Israel
facility: Rambam Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Roma
country: Italy
facility: Ospedale Pedriatrico Bambino Gesù
city: via Oxford 81, Roma
country: Italy
facility: Universita di Roma Tor Vergata
city: Viale Morgagni, Florence
country: Italy
facility: Ospedale di Careggi BMT Unit Department of Haematology
city: Avda. Blasco Ibañez, 17, Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
state: Comunidad Valenciana
city: Av Campanar 21, Valencia
country: Spain
facility: Hospital Universitario La Fe
city: C/ Sant Antoni Maria Claret, Barselona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Carretera de Canyet s/n, Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Doctor Esquerdo 46 , Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Passeig de la Vall d´Hebrón 119-129, Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebrón (Pediatrics)
city: Passeig de la Vall d´Hebrón 119-129, Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebrón
Study officials:
affiliation: Texas Transplant Institute
name: Ka Wah Chan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cancer Center at Hackensack University Medical Center
name: Scott D Rowley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCLA Oncology Center
name: Mary Territo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola University Cardinal Bernardin Cancer Center
name: Patrick Stiff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Cancer Institute/UPMC Cancer Centers
name: Agha Mounzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Western Pennsylvania Hospital
name: Entezam Sahovic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Celia Grosskreutz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Children's Hospital, B115, University of Colorado Health Sciences Center
name: Roger Giller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Orange County
name: Steven Neudorf, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chaim Sheba Medical Center
name: Ronit Yerushalmi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rambam Health Care Campus
name: Tsila Zuckerman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germans Trias i Pujol Hospital
name: Christelle Ferra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario de Valencia
name: Cristina Arbona, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Fe
name: Guillermo Sanz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universita di Roma Tor Vergata
name: William Arcese, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di Careggi BMT Unit Department of Haematology
name: Alberto Bosi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital
name: Sonali Chaudhury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Jorge Sierra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Bone Marrow Transplantation And Cancer Immunotherapy Hebrew University Hospital Ein-Karem, Jerusalem
name: Igor B. Resnick, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Pedriatrico Bambino Gesù
name: Prof. Franco Locatelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario Gregorio Marañón
name: Dr. Mi Kwon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Vall d´Hebrón
name: Dr. Pere Barba, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Vall d´Hebrón
name: Dr. Cristina Diaz de Heredia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hematopoietic Stem Cell Transplant Program, University of Virginia
name: Prof. Mary J Laughlin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1046/j.0007-1048.2001.03316.x.
citation: 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. doi: 10.1016/j.exphem.2004.03.002.
citation: 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. doi: 10.1080/10428190310001598035.
citation: 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. doi: 10.1080/14653240410004916.
citation: 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. doi: 10.1016/j.exphem.2005.06.015.
citation: Shpall EJ, M.d.L., K. Chan, R. Champlin, A. Gee, P. Thall, K. Komanduri, D. Couriel, C. Hosing, B. Andersson, R. Jones, S. Giralt, S. Karandish, T. Sadeghi, B. Muriera, S. O'Connor, L. Wooten, X. Wang, S. Robinson, P. Fu, J. Wilson, T. Peled, F. Grynspan, A. Nagler, J. McMannis; A Phase I/II Study of Ex Vivo Expanded Cord Blood for Leukemia and Lymphoma. ISCT 2005 - conference publication, 2005.
citation: 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. doi: 10.1038/sj.bmt.1705979. Epub 2008 Jan 21.
citation: Stiff PJ, Montesinos P, Peled T, Landau E, Goudsmid NR, Mandel J, Hasson N, Olesinski E, Glukhman E, Snyder DA, Cohen EG, Kidron OS, Bracha D, Harati D, Ben-Abu K, Freind E, Freedman LS, Cohen YC, Olmer L, Barishev R, Rocha V, Gluckman E, Horowitz MM, Eapen M, Nagler A, Sanz G. Cohort-Controlled Comparison of Umbilical Cord Blood Transplantation Using Carlecortemcel-L, a Single Progenitor-Enriched Cord Blood, to Double Cord Blood Unit Transplantation. Biol Blood Marrow Transplant. 2018 Jul;24(7):1463-1470. doi: 10.1016/j.bbmt.2018.02.012. Epub 2018 Mar 1.