A Phase II Study of Umbilical Cord Blood Transplantation - Full Text View

Sponsor:	Tufts Medical Center
Information provided by:	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00676806

Purpose

This study is designed to determine whether Umbilical Cord Transplantation (UCB) can be substituted for adult bone marrow cells in the standard stem cell transplant regimens used at this hospital for subjects who do not have stem cell donors.

Condition	Intervention	Phase
Leukemia Lymphoma Multiple Myeloma Aplastic Anemia	Biological: Umbilical Cord Blood Transplantation After Myeloablative Conditioning Biological: Umbilical Cord Blood Transplantation After Reduced-Intensity Conditioning	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study of Umbilical Cord Blood Transplantation Following Myeloablative or Reduced-Intensity Conditioning

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Anemia Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:

Determine the rate of neutrophil engraftment in adult patients receiving umbilical cord blood for hematopoietic rescue following myeloablative or non-myeloablative conditioning. [ Time Frame: +45 and 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine the rate of platelet engraftment measured as the median time to platelet engraftment and the Kaplan-Mayer estimate of proportion of patients engrafting by days +45, 90 and 180.. [ Time Frame: +45, 90 and 180 days ] [ Designated as safety issue: Yes ]
Evaluate the incidence of acute and chronic GVHD [ Time Frame: Day +100, ongoing ] [ Designated as safety issue: Yes ]
Compare rates of engraftment and complications between patients receiving ablative vs. non-myeloablative conditioning prior to UCB transplantation. [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
Evaluate infectious complications in UCB recipients. [ Time Frame: Day +100, ongoing ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	July 2005
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Adult patients receiving umbilical cord blood for hematopoietic rescue following myeloablative conditioning	Biological: Umbilical Cord Blood Transplantation After Myeloablative Conditioning Fully-myeloablative Conditioning Regimen: cyclophosphamide (60mg/m2 days -6 & -5), fludarabine (25 mg/m2 days -7, -6, & -5) and total body irradiation (days -3, -2, & -1, total 1200 cGy) followed by cord blood infusion on day 0.
2: Experimental Adult patients receiving umbilical cord blood for hematopoietic rescue following non-myeloablative conditioning	Biological: Umbilical Cord Blood Transplantation After Reduced-Intensity Conditioning Reduced Intensity Conditioning Regimen: Extracorporeal Photopheresis (days -8 & -7), cyclophosphamide 50 mg/kg (day -6) pentostatin 4 mg/kg/d (continuous infusion days -5 & -4), total body irradiation (days -3 & -2, total 600cGy) followed by Umbilical Cord Blood Infusion day 0.

Detailed Description:

Allogeneic stem cell transplantation (SCT) following myeloablative and non-myeloablative conditioning therapy has proven curative treatment for a number of inherited and acquired hematologic disorders. The success of allogeneic transplantation is largely determined by compatibility between donor and recipient, which predicts the risk of fatal graft-versus-host disease (GVHD). Unfortunately, less than one third of patients needing an allogeneic transplant have an available compatible donor in their family. Registries have been established to match patients with compatible volunteer (unrelated) donors, but many patients, and in particular minority patients, still lack stem cell donors.

Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, which is readily available from the placenta following childbirth. Blood banks have been established in the United States and abroad to collect, process and store UCB for use in allogeneic transplantation. To date, more than 2000 UCB transplants have been performed in adults and children around the world.

Rationale for use of Umbilical Cord Blood in Transplantation

UCB has a number of proven and theoretical advantages as an alternative source of hematopoietic stem cells for transplantation:

Placental or umbilical cord blood is an abundantly available source of stem cells, which is currently discarded and can be harvested at no risk to the mother or infant.
Important infectious agents, particularly CMV, are much less common in the newborn than adults, and are less likely to contaminate UCB collections.
UCB collections, typed, cryopreserved and banked, are available on demand, eliminating delays and uncertainties that now complicate marrow collection from unrelated donors. At present, UCB can be delivered for infusion within days of the initiation of a search. This compares with a median of 3 months from search to delivery of stem cells through the registries of volunteer adult donors.
The intensity of graft-versus-host reactivity of fetal lymphocytes appears to be less than that of adult cells and consequently fetal lymphocytes are more tolerant of HLA incompatibility. Published studies have shown that transplantation of UCB matched at 4-5/6 antigens results in a comparable incidence of GVHD to transplantation of unrelated stem cells fully matched at 6/6 antigens.
Frozen UCB can be easily shipped, stored at the treating institution, and thawed for use when needed, compared to freshly donated stem cells which have a limited shelf-life of one day or less, necessitating coordination between harvesting surgeons, transportation, and transplantation teams.

This research study has been designed for people who have been diagnosed with a blood tumor, which has not responded to treatment or has recurred, a bone marrow failure state such as aplastic anemia, or one of certain inherited metabolic disorders; and whose doctor feels the best treatment is an allogeneic stem cell transplant (alloSCT) but a related or unrelated adult donor is not available. Instead, a single unit of umbilical cord blood (UCB) will be used as the source of the subject's immune system. This study is designed to determine whether a single unit of UCB can be substituted for adult bone marrow cells in the standard stem cell transplant regimens used at this hospital for subjects who do not have stem cell donors.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients meeting eligibility criteria for unrelated allogeneic stem cell transplantation may be considered for participation on this clinical trial if and only if they meet each of the following criteria:

Patients must have one of the following diagnoses
Relapsed or refractory hematologic malignancy, or
High risk hematologic malignancy in first remission, or
Refractory acquired marrow failure state, or
Inherited disorder of metabolism or marrow failure state without alternative curative therapy.
Patients must not have a 6/6 or 5/6 HLA-matched related donor.
Patients must not have a HLA-A, -B and -DRB1 high resolution matched unrelated donor following registry search, or cannot (in the opinion of the treating physician) wait the median 3 months to receive a MUD unit.
Patients must demonstrate an ability to understand and willingness to sign the informed consent document

Patients considered for myeloablative conditioning must satisfy the following additional criteria:

Patients must be between the ages of 18 and 55 (inclusive)
Patients must have serum direct bilirubin ≤ 2.0 mg/dl and transaminases ≤ 2x institution upper limit of normal
Patients must have serum creatinine ≤ 2 mg/dl with creatinine clearance ≥ 60 ml/min (either calculated or measured).
Patients must have MUGA scan or echocardiogram normal for the institution, but not less than 45% left ventricular ejection fraction and no clinical evidence of cardiac dysfunction.
Patients must have an ECOG performance status of 0 or 1 (see Appendix C).
Patients must have adequate pulmonary function when corrected for hemoglobin and alveolar volume as evidenced by a diffusion capacity and FEV1 > 50% of predicted.

Patients considered for reduced-intensity conditioning must satisfy the following additional criteria:

Patients must not be candidates for myeloablative conditioning due to any one of the following
Prior myeloablative stem cell transplantation
Age > 50
Co morbid illness
In opinion of treating physician, unable to comply with or withstand rigors of myeloablative conditioning

v Patients with leukemia must have circulating and bone marrow blast counts < 5%, all other patients must have chemotherapy responsive disease v Patients must be between the ages of 18 and 70 (inclusive) v Patients must have serum direct bilirubin ≤ 2.0 mg/dL and transaminases ≤ 3x institution upper limit of normal v Patients must have creatinine clearance ≥ 30 ml/min (either calculated or measured).

v Patients must have MUGA scan or echocardiogram documenting left ventricular ejection fraction of no less than 35% and no clinical evidence of cardiac dysfunction.

v Patients must have an ECOG performance status of 0 or 1 (see Appendix C). v Patients must have adequate pulmonary function when corrected for hemoglobin and alveolar volume as evidenced by a diffusion capacity and FEV1 ≥ 40% of predicted.

Exclusion Criteria:

Patients are ineligible for participation on this trial if they meet any of the following criteria:

Patients with a history of myocardial infarction within the preceding 6 months, significant arrhythmia within the preceding 3 months, uncontrolled hypertension or congestive heart failure are ineligible.
Patients with unstable angina are not eligible.
Pregnant or lactating women are ineligible.
Male and female patients who do not agree to practice approved methods of birth control for the duration of the study are ineligible.
Patients with uncontrolled infection are ineligible.
Patients who are HIV positive or have evidence of chronic viral hepatitis are ineligible.
Patients unable to comply with requirements for compliance with therapeutic plan and/or scheduled evaluations

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00676806

Contacts

Contact: Andreas Klein, MD	617.636.2520 ext 6-2520	aklein2@tuftsmedicalcenter.org
Contact: Carrie Grodman, RN	617.636.2682 ext 6-2682	cgrodman@tuftsmedicalcenter.org

Locations

United States, Massachusetts
Tufts Medical Center	Recruiting
Boston, Massachusetts, United States, 02111
Contact: Andreas Klein, MD 617-636-2520 ext 6-2520 aklein2@tuftsmedicalcenter.org
Contact: Carrie Grodman, RN 617.636.2682 ext 6-2682 cgrodman@tuftsmedicalcenter.org
Principal Investigator: Andreas Klein, MD
Sub-Investigator: Kellie Sprague, MD
Sub-Investigator: Hans Klingemann, MD

Sponsors and Collaborators

Tufts Medical Center

Investigators

Principal Investigator:

Andreas Klein, MD

Tufts Medical Center

More Information

Additional Information:

Cancer Center at Tufts Medical Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Tufts Medical Center ( Andreas Klein, MD, Assistant Professor of Medicine )
Study ID Numbers:	UCBT001
Study First Received:	May 9, 2008
Last Updated:	October 13, 2009
ClinicalTrials.gov Identifier:	NCT00676806 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Tufts Medical Center:

Umbilical cord blood transplantation
full ablation conditioning
reduced intensity conditioning

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Blood Protein Disorders
Hematologic Diseases
Vascular Diseases
Anemia
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma

Leukemia
Lymphatic Diseases
Neoplasms
Hemorrhagic Disorders
Anemia, Aplastic
Cardiovascular Diseases
Bone Marrow Diseases
Lymphoproliferative Disorders
Lymphoma
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on February 08, 2010