A Phase II Study of Umbilical Cord Blood Transplantation
|Leukemia Lymphoma Multiple Myeloma Aplastic Anemia||Biological: Umbilical Cord Blood After Myeloablative Conditioning Biological: Umbilical Cord Blood After Reduced-Intensity Conditioning||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Umbilical Cord Blood Transplantation Following Myeloablative or Reduced-Intensity Conditioning|
- Number of Participants With Neutrophil Engraftment [ Time Frame: +45 and 90 days ]Number of participants with neutrophil engraftment receiving umbilical cord blood for hematopoietic rescue following myeloablative or non-myeloablative conditioning
- Proportion of Subjects With Platelet Engraftment [ Time Frame: +45, 90, and 180 days ]Proportion of patients engrafting by days +45, +90, and +180.
- Incidence of Acute GVHD [ Time Frame: Day +100 ]
- Infectious Complications in UCB Recipients. [ Time Frame: Day +100 ]
- Incidence of Chronic GVHD [ Time Frame: After Day +100 ]
- Compare Rates of Complications Between Patients Receiving Ablative vs. Non-myeloablative Conditioning Prior to UCB Transplantation [ Time Frame: +180 days ]Composite endpoint of GVH or infection. Too few events to compare between arms.
|Study Start Date:||July 2005|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Myeloablative conditioning
Umbilical cord blood for hematopoietic rescue following myeloablative conditioning
Biological: Umbilical Cord Blood After Myeloablative Conditioning
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.
Experimental: Reduced intensity conditioning
Umbilical cord blood for hematopoietic rescue following non-myeloablative conditioning
Biological: Umbilical Cord Blood After Reduced-Intensity Conditioning
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00676806
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Principal Investigator:||Andreas Klein, MD||Tufts Medical Center|