Cord Blood Stem Cell Transplantation Study (COBLT)

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Brief Title

Cord Blood Stem Cell Transplantation Study (COBLT)


Brief Summary

      To evaluate if HLA-mismatched, unrelated-donor umbilical cord blood stem and progenitor cell
      units (UCBU) offered a clinically acceptable alternative to matched unrelated-donor
      allogeneic bone marrow for transplantation with 180-day disease free survival as the
      endpoint. HLA typing was performed using DNA-base high resolution methods to determine HLA
      alleles. Patients with "true" HLA 3/6 and 4/6 matches were evaluated. In addition, a separate
      study in adults addressed the problem of limited cell dose and engraftment failure. The study
      was not planned as a randomized comparative clinical trial. Instead, it is a phase II/III
      efficacy study.
    

Detailed Description

      BACKGROUND:

      Bone marrow transplantation is an effective therapy for a variety of genetic and hematologic
      disorders. Donated bone marrow, which provides a source of stem and progenitor cells for bone
      marrow reconstitution, is obtained either from related donors, usually HLA-matched siblings,
      or from HLA-matched unrelated donors. Because of the limited availability of HLA-matched
      related donors, HLA-matched unrelated donors are frequently the only alternative source of
      bone marrow for transplantation. To provide matched volunteer bone marrow donors for
      unrelated recipients, the National Marrow Donor Program (NMDP) was established in 1986 to
      develop a national Registry of HLA-typed individuals who agree to donate bone marrow if
      needed. More than 3 million potential marrow donors are now enrolled. A limitation of the
      registry approach is the time needed to identify a donor and complete the necessary clinical
      evaluation and laboratory testing for histocompatibility, infectious diseases, and general
      good health. Moreover, a certain proportion of potential donors change their minds or
      otherwise become unavailable between the time they enter the Registry and the time they are
      called as a preliminary match for a patient. Another disadvantage is the marrow harvesting
      procedure which requires the normal donor to be hospitalized and given general anesthesia in
      an operating room. Finally, the NMDP Registry consists of potential donors that are primarily
      of European Caucasian ancestry. Although great strides have been made in increasing the
      numbers of African-Americans, Hispanics, Asian-Americans, and Native Americans, it is still
      more difficult to find matches for these ethnic minorities than for Caucasian patients.

      Human umbilical cord blood is an alternative source of hematopoietic stem and progenitor
      cells capable of reconstituting the bone marrow of recipients with a variety of diseases.
      Cord blood stem and progenitor cells from related donors have been successfully transplanted
      world-wide in children with genetic or hematologic diseases. These results suggested that
      cord blood from unrelated, HLA-matched donors also can be used for patients who need a
      transplant but don't have a related donor. The existing problems in unrelated-donor bone
      marrow transplantation with donor recruitment, bone marrow harvesting, and matching for
      antigens peculiar to a particular ethnic group would be reduced if typed, tested, and frozen
      umbilical cord blood could be made easily and rapidly available. Such a system, which could
      complement or partially replace the present process, has been shown to be feasible. In an
      NHLBI-sponsored program, investigators have collected and cryopreserved a bank of about 9,000
      human UCBUs. In addition, successful searches and matches (including many 4/6 antigen
      matches) have resulted in more than 900 unrelated-donor, UCBU transplants to date.
      Preliminary data from both these unrelated-donor and other related-donor cord blood
      transplants suggest that there is less GvHD than if the source of the graft were adult bone
      marrow. The severity of GvHD also seems less even in highly mismatched recipients. One
      important question is whether or not 3/6 HLA matched transplants in children will have
      acceptable 180-day disease free survival. It also remains to be determined if the
      graft-vs-leukemia effect is also less or if unrelated-donor cord blood grafts are as durable
      as those from matched, related-donors. Most transplants conducted thus far have been in
      children. Hence another important question is whether or not there are sufficient numbers of
      stem cells in cord blood to support transplantation to an unrelated adult.

      The initiative was proposed by the Division of Blood Diseases and Resources staff and
      approved by the February 1995 National Heart, Lung, and Blood Advisory Council. The Requests
      for Proposals were released in June 1995. Contracts were awarded September 30, 1997.

      DESIGN NARRATIVE:

      The study is multicenter, with six Cord Blood Transplant Centers (CBTCs), two collecting and
      storage centers (Cord Blood Banks -- CBBs) and one Coordinating Center. Each CBB used the
      same protocol for recruiting donors, collecting, processing, testing, storage, retrieval from
      storage, reprocessing from the frozen state, and shipping. Each participating CBTC used the
      same patient selection criteria, preparative regimen for patients in the same class, initial
      graft-versus-host disease (GvHD) prophylaxis, indications for the use of cytokines,
      definitions for events and complications, and methods for evaluating immune reconstitution.
      The main study evaluated the impact of HLA 3/6 and 4/6 matching on outcome. The primary
      endpoint was 180-day disease free survival after UCBU transplantation. Secondary endpoints
      included engraftment, the frequency and severity of acute and chronic GvHD with
      stratification by degree of HLA match, overall survival, and immunologic reconstitution. Data
      were collected on banked UCBUs to define unit quality by nucleated cell count and flow
      cytometry of surface markers to identify effects on patient outcome. Recruitment ended
      December 31, 2003 with the accrual of 326 subjects. .
    

Study Phase

Phase 2

Study Type

Interventional




Condition

Anemia, Aplastic

Intervention

stem cell transplantation


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure


Start Date

September 1996

Completion Date

October 2007

Primary Completion Date

October 2007

Eligibility Criteria

        Mothers of Infant-donors must complete a medical history form, have an uncomplicated
        delivery, and deliver at UCLA or Duke.

        Patients are those who need a transplant but don't have a matched marrow donor or can't
        wait to find one.
      

Gender

All

Ages

N/A - 55 Years

Accepts Healthy Volunteers

No

Contacts

Shelly Carter, , 



Administrative Informations


NCT ID

NCT00000603

Organization ID

316



Study Sponsor

National Heart, Lung, and Blood Institute (NHLBI)


Study Sponsor

Shelly Carter, , The Emmes Company, LLC


Verification Date

January 2008