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

Sponsor

Gamida Cell -Teva Joint Venture Ltd. (Other)

Overall Status

Completed

CT.gov ID

NCT00469729

Collaborator

(none)

101

Enrollment

Locations

Arm

Duration (Months)

3.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies Acute Myeloid Leukemia Lymphoid Leukemia Chronic Myeloid Leukemia Hodgkin's Disease Non-Hodgkin's Lymphoma Myelodysplastic Syndromes	Drug: StemEx®	Phase 2/Phase 3

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:

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)

Study Design

Study Type:

Interventional

Actual Enrollment :

101 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: StemEx	Drug: StemEx® 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.

Arm

Intervention/Treatment

Experimental: StemEx

Drug: StemEx®

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.

Outcome Measures

Primary Outcome Measures

Overall 100-day mortality [100 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA's Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095-1781
2	Children's Hospital of Orange County	Orange	California	United States	92868-3874
3	The Children's Hospital, B115, University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
4	Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital	Chicago	Illinois	United States	60614
5	Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine	Maywood	Illinois	United States	60153
6	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	Cornell University, Joan & Sanford I. Weill Medical College	New York	New York	United States	NY 10065
8	Steven and Alexandra Cohen Children's Medical Center of New York	New York	New York	United States
9	Mount Sinai Medical Center	One Gustave L Levy Place, BOX 1410, New York	New York	United States	10029
10	Case Western Reserve University	Cleveland	Ohio	United States	44106
11	The Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
12	University of Pittsburgh Cancer Institute/UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
13	Texas Transplant Institute	San Antonio	Texas	United States	78229
14	University of Virginia, Hematopoietic Stem Cell Transplant Program	West Complex 1300 Jefferson Park Av, Charlottesville	Virginia	United States	22903
15	Medical College of Wisconsin Division of Neoplastic Diseases and Related Disorders	Milwaukee	Wisconsin	United States	53226
16	Medical College of Wisconsin Pediatric Blood and Marrow Transplant Program	Milwaukee	Wisconsin	United States	53226
17	Szent Laszlo & Szent Istvan Hospital	Budapest		Hungary	1097
18	Hebrew University Hospital Ein-Karem, Department of Bone Marrow Transplantation And Cancer Immunotherapy	Jerusalem		Israel	P.O.B 12000
19	Rambam Medical Center	PO Box 9602, Haifa		Israel	31096
20	Chaim Sheba Medical Center	Tel Hashomer		Israel	52621
21	Ospedale Pedriatrico Bambino Gesù	Roma		Italy	00165
22	Universita di Roma Tor Vergata	via Oxford 81, Roma		Italy	00133
23	Ospedale di Careggi BMT Unit Department of Haematology	Viale Morgagni, Florence		Italy	85 - 50134
24	Hospital Clínico Universitario de Valencia	Avda. Blasco Ibañez, 17, Valencia	Comunidad Valenciana	Spain	46010
25	Hospital Universitario La Fe	Av Campanar 21, Valencia		Spain	46009
26	Hospital de la Santa Creu i Sant Pau	C/ Sant Antoni Maria Claret, Barselona		Spain	167 - 08025
27	Hospital Germans Trias i Pujol	Carretera de Canyet s/n, Badalona		Spain	08916
28	Hospital General Universitario Gregorio Marañón	Doctor Esquerdo 46 , Madrid		Spain	28007
29	Hospital Universitario Vall d´Hebrón (Pediatrics)	Passeig de la Vall d´Hebrón 119-129, Barcelona		Spain	08035
30	Hospital Universitario Vall d´Hebrón	Passeig de la Vall d´Hebrón 119-129, Barcelona		Spain	08035

Sponsors and Collaborators

Gamida Cell -Teva Joint Venture Ltd.

Investigators

Principal Investigator: Ka Wah Chan, MD, Texas Transplant Institute
Principal Investigator: Scott D Rowley, MD, The Cancer Center at Hackensack University Medical Center
Principal Investigator: Mary Territo, MD, UCLA Oncology Center
Principal Investigator: Patrick Stiff, MD, Loyola University Cardinal Bernardin Cancer Center
Principal Investigator: Agha Mounzer, MD, University of Pittsburgh Cancer Institute/UPMC Cancer Centers
Principal Investigator: Entezam Sahovic, MD, The Western Pennsylvania Hospital
Principal Investigator: Celia Grosskreutz, MD, Icahn School of Medicine at Mount Sinai
Principal Investigator: Roger Giller, MD, The Children's Hospital, B115, University of Colorado Health Sciences Center
Principal Investigator: Steven Neudorf, MD, Children's Hospital of Orange County
Principal Investigator: Ronit Yerushalmi, MD, Chaim Sheba Medical Center
Principal Investigator: Tsila Zuckerman, MD, Rambam Health Care Campus
Principal Investigator: Christelle Ferra, MD, Germans Trias i Pujol Hospital
Principal Investigator: Cristina Arbona, MD, Hospital Clínico Universitario de Valencia
Principal Investigator: Guillermo Sanz, MD, Hospital Universitario La Fe
Principal Investigator: William Arcese, MD, Universita di Roma Tor Vergata
Principal Investigator: Alberto Bosi, MD, Ospedale di Careggi BMT Unit Department of Haematology
Principal Investigator: Sonali Chaudhury, MD, Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital
Principal Investigator: Jorge Sierra, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Principal Investigator: Igor B. Resnick, MD, PhD, Department of Bone Marrow Transplantation And Cancer Immunotherapy Hebrew University Hospital Ein-Karem, Jerusalem
Principal Investigator: Prof. Franco Locatelli, MD, Ospedale Pedriatrico Bambino Gesù
Principal Investigator: Dr. Mi Kwon, MD, Hospital General Universitario Gregorio Marañón
Principal Investigator: Dr. Pere Barba, MD, Hospital Universitario Vall d´Hebrón
Principal Investigator: Dr. Cristina Diaz de Heredia, MD, Hospital Universitario Vall d´Hebrón
Principal Investigator: Prof. Mary J Laughlin, MD, Hematopoietic Stem Cell Transplant Program, University of Virginia