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

NCT ID: NCT00469729

Last Updated: 2015-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2015-06-30

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)

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

StemEx

Group Type: EXPERIMENTAL

StemEx®

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gamida Cell -Teva Joint Venture Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ka Wah Chan, MD

Role: PRINCIPAL_INVESTIGATOR

Texas Transplant Institute

Scott D Rowley, MD

Role: PRINCIPAL_INVESTIGATOR

The Cancer Center at Hackensack University Medical Center

Mary Territo, MD

Role: PRINCIPAL_INVESTIGATOR

UCLA Oncology Center

Patrick Stiff, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University Cardinal Bernardin Cancer Center

Agha Mounzer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Cancer Institute/UPMC Cancer Centers

Entezam Sahovic, MD

Role: PRINCIPAL_INVESTIGATOR

The Western Pennsylvania Hospital

Celia Grosskreutz, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Roger Giller, MD

Role: PRINCIPAL_INVESTIGATOR

The Children's Hospital, B115, University of Colorado Health Sciences Center

Steven Neudorf, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Orange County

Ronit Yerushalmi, MD

Role: PRINCIPAL_INVESTIGATOR

Chaim Sheba Medical Center

Tsila Zuckerman, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus

Christelle Ferra, MD

Role: PRINCIPAL_INVESTIGATOR

Germans Trias i Pujol Hospital

Cristina Arbona, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clínico Universitario de Valencia

Guillermo Sanz, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Fe

William Arcese, MD

Role: PRINCIPAL_INVESTIGATOR

Universita di Roma Tor Vergata

Alberto Bosi, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale di Careggi BMT Unit Department of Haematology

Sonali Chaudhury, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital

Jorge Sierra, MD

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Igor B. Resnick, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Bone Marrow Transplantation And Cancer Immunotherapy Hebrew University Hospital Ein-Karem, Jerusalem

Prof. Franco Locatelli, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Pedriatrico Bambino Gesù

Dr. Mi Kwon, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón

Dr. Pere Barba, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Vall d´Hebrón

Dr. Cristina Diaz de Heredia, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Vall d´Hebrón

Prof. Mary J Laughlin, MD

Role: PRINCIPAL_INVESTIGATOR

Hematopoietic Stem Cell Transplant Program, University of Virginia

Locations

UCLA's Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

The Children's Hospital, B115, University of Colorado Health Sciences Center

Aurora, Colorado, United States

Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital

Chicago, Illinois, United States

Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine

Maywood, Illinois, United States

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Cornell University, Joan & Sanford I. Weill Medical College

New York, New York, United States

Steven and Alexandra Cohen Children's Medical Center of New York

New York, New York, United States

Mount Sinai Medical Center

One Gustave L Levy Place, BOX 1410, New York, New York, United States

Case Western Reserve University

Cleveland, Ohio, United States

The Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Institute/UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Texas Transplant Institute

San Antonio, Texas, United States

University of Virginia, Hematopoietic Stem Cell Transplant Program

West Complex 1300 Jefferson Park Av, Charlottesville, Virginia, United States

Medical College of Wisconsin Division of Neoplastic Diseases and Related Disorders

Milwaukee, Wisconsin, United States

Medical College of Wisconsin Pediatric Blood and Marrow Transplant Program

Milwaukee, Wisconsin, United States

Szent Laszlo & Szent Istvan Hospital

Budapest, , Hungary

Hebrew University Hospital Ein-Karem, Department of Bone Marrow Transplantation And Cancer Immunotherapy

Jerusalem, , Israel

Rambam Medical Center

PO Box 9602, Haifa, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Ospedale Pedriatrico Bambino Gesù

Roma, , Italy

Universita di Roma Tor Vergata

Via Oxford 81, Roma, , Italy

Ospedale di Careggi BMT Unit Department of Haematology

Viale Morgagni, Florence, , Italy

Hospital Clínico Universitario de Valencia

Avda. Blasco Ibañez, 17, Valencia, Valencia, Spain

Hospital Universitario La Fe

Av Campanar 21, Valencia, , Spain

Hospital de la Santa Creu i Sant Pau

C/ Sant Antoni Maria Claret, Barselona, , Spain

Hospital Germans Trias i Pujol

Carretera de Canyet S/n, Badalona, , Spain

Hospital General Universitario Gregorio Marañón

Doctor Esquerdo 46 , Madrid, , Spain

Hospital Universitario Vall d´Hebrón (Pediatrics)

Passeig de La Vall d´Hebrón 119-129, Barcelona, , Spain

Hospital Universitario Vall d´Hebrón

Passeig de La Vall d´Hebrón 119-129, Barcelona, , Spain

Countries

United States; Hungary; Israel; Italy; Spain

References

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.

Reference Type: BACKGROUND

PMID: 11849228 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15183895 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15160922 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16146887 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16219531 (View on PubMed)

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 18209724 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29477778 (View on PubMed)

Related Links

http://www.gamida-cell.com/

Sponsor's website

http://www.lymphomation.org

Patients Against Lymphoma

http://www.bmtinfonet.org/

Bone and Marrow Transplant Information Network

http://www.cancer.gov/cancertopics/types/leukemia

NCI Leukemia Homepage

http://www.medicinenet.com/leukemia/article.htm

Leukemia information on MediciNet.com

http://www.asbmt.org/

American Society for Blood and Marrow Transplantation

http://www.hematology.org/

American Society of Hematology

http://www.lymphoma.org

Lymphoma Research Foundation

http://www.cancer.org/docroot/home/index.asp

American Cancer Society website

http://www.cibmtr.org/

Center for International Blood and Marrow Transplant Research

http://www.marrow.org/

National Marrow Donor Program

http://www.choc.org/

Children's Hospital of Orange County

http://www.childrensmemorial.org/depts/stemcell/overview.aspx

Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital website

http://medschool.duke.edu/

Duke University Medical Center

http://www.case.edu/

Case Western Reserve University

http://www.upmccancercenters.com/

University of Pittsburgh Cancer Institute

http://www.mdanderson.org/

MD Anderson Cancer Center

http://www.texastransplant.org/

Texas Transplant Institute

http://www.chu-stlouis.fr/

Hôpital Saint Louis

http://eng.sheba.co.il/

Chaim Sheba Medical Center

http://www.rambam.org.il/

Rambam Medical Center

http://web.uniroma2.it/home.php?sr=1024

Universita di Roma Tor Vergata

http://www.aou-careggi.toscana.it/internet/index.php

Ospedale di Careggi BMT Unit Department of Haematology

http://www.gencat.net/ics/germanstrias/

Hospital Germans Trias i Pujol

http://www.hospitalclinic.org/

Hospital Clinic of Barcelona

http://www.santpau.es/

Hospital de la Santa Creu i Sant Pau

http://www.ucla.edu/

ULCA

Other Identifiers

GC P#02.01.001

Identifier Type: -

Identifier Source: org_study_id

NCT00763334

Identifier Type: -

Identifier Source: nct_alias