Cord Blood Transplantation for Sickle Cell Anemia and Thalassemia

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00029380

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will develop a national cord blood bank for siblings of patients with hemoglobinopathies and thalassemia.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Diseases Anemia, Sickle Cell Beta-Thalassemia Hematopoietic Stem Cell Transplantation	Drug: Sangstat Drug: Cyclophosphamide Drug: Busulfan Drug: Mycophenolate Mofetil Drug: Cyclosporine Procedure: Cord Blood Transplantation	Phase 2

Detailed Description

BACKGROUND:

During the past decade, a number of advances have been made in the treatment of patients with sickle cell anemia and thalassemia. Among these advances is allogeneic bone marrow transplantation, which is the only current treatment that offers a potential for cure. In sickle cell anemia, transplantation has been performed in patients who have had advanced organ damage. In thalassemia, transplantation has been performed before having any evidence of iron-related tissue damage. Due to concerns over engraftment and graft versus host disease (GVHD), transplants for patients with hemoglobinopathies have been limited to situations in which a human leukocyte antigen (HLA) compatible donor existed. Unfortunately, an HLA-matched related donor is often not available. Umbilical cord blood (UCB), a recently recognized source of hematopoietic stem cells, has been used to successfully transplant bone marrow to over 500 patients. The potential advantage of cord blood over other donor sources of stem cells is the minimal risk of high-grade GVHD (even without complete HLA compatibility).

DESIGN NARRATIVE:

This study will establish a national sibling donor cord blood (SDCB) program, evaluate its use in a multi-center pilot study of transplantation, and develop a Web-based data management system to support these two projects. A multi-center pilot study was conducted on cord blood transplantation in children with either sickle cell disease or thalassemia. The investigators tested the hypothesis that a novel immunosuppressive conditioning regimen (fludarabine, cyclophosphamide, and busulfan) and post transplant therapy (mycophenolate mofetil and cyclosporine) would improve engraftment rates and prevent disease recurrence. The effect of SDCB transplantation on hematologic parameters and GVHD was monitored. Enrollment in the study was suspended on December 29, 2003. The protocol was revised, replacing the previous conditioning regimen of fludarabine, busulfan, and cyclophosphamide with a more conventional regimen of rabbit anti-thymocyte globulin (Sangstat), busulfan, and cyclophosphamide. The revised protocol is open for enrollment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Primary Purpose:

Treatment

Official Title:

Sibling Donor Cord Blood Banking and Transplantation

Study Start Date :

Jan 1, 1999

Actual Primary Completion Date :

Aug 1, 2006

Actual Study Completion Date :

Aug 1, 2006

Outcome Measures

Primary Outcome Measures

Hematologic parameters []
GVHD []

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Suitable UCB collection from an HLA-identical sibling
Sickle cell anemia (Hb SS or S beta thalassemia) with significant disease manifestations as defined by at least one of the following criteria:

A history of painful events defined as three or more painful events in the 2 years prior to enrollment. Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than sickle cell disease. The pain must last at least 4 hours and require treatment with either parenteral narcotics, an equianalgesic dose of oral narcotics (if pain is treated in a local facility where parenteral narcotics are not routinely used to treat painful events), or parenteral nonsteroidal anti-inflammatory drugs. Painful events managed at home will be considered only if there is documentation of the event in a clinical record that may be reviewed by an investigator.
Acute chest syndrome (ACS) with two or more episodes of ACS with the development of a new infiltrate on chest radiograph and/or having a perfusion defect demonstrable on a lung radioisotope scan
Any combination of painful events and episodes of ACS that total three events in the 2 years before transplantation
Any clinically significant neurologic event (stroke or hemorrhage) or any neurologic defect lasting more than 24 hours
Abnormal cerebral MRI and abnormal cerebral MRA
An episode of dactylitis in the first year of life with significant anemia (Hbg less than 7 g/dL), or leukocytosis in the second year of life such that the risk of a severe adverse outcome before 18 years of age exceeds 54% (as defined by the cooperative study of sickle cell disease (CSSCD) infant cohort study)
History of positive trans-cranial Doppler studies (average greater than 200 cm/sec)

Beta thalassemia major with significant disease manifestations as defined by the following criteria: Beta thalassemia genotype consistent with clinical diagnosis of beta thalassemia major (could include patients with E-beta thalassemia genotype) and requiring eight or more red blood cell (RBC) transfusions a year and iron chelation therapy. Younger patients who are at risk of transfusional iron overload but who have not yet initiated iron chelation therapy will be eligible.
Adequate physical function as measured by the following criteria:

Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be greater than 40% and must improve with exercise, or shortening fraction greater than 26%
Hepatic: Less than 5 times the clinical baseline of AST and less than 2.5 times the clinical baseline mg/dL of total serum bilirubin (clinical baseline is determined from the mean of the four most recent test results)
Renal: Serum creatinine within normal range for age or if serum creatinine is outside normal range for age then renal function (creatinine clearance or GFR) greater than 50% of the lower limit of normal (LLN) for age
Pulmonary: Asymptomatic, or, if symptomatic, DLCO, FEV1, FEC (diffusion capacity) greater than 45% of predicted (corrected for hemoglobin); if unable to obtain PFT, oxygen saturation greater than 85% on room air

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Oakland	Oakland	California	United States	94609
2	Children's Hospital, Oakland	Oakland	California	United States	94609
3	Children's National Medical Center	Washington	District of Columbia	United States
4	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
5	University of Miami Batchelor Children's Research Center	Miami	Florida	United States	33136
6	Children's Memorial Hospital	Chicago	Illinois	United States	60614
7	Louisiana State University Children's Medical Center	New Orleans	Louisiana	United States
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
10	Duke University Medical Center Children's Hospital	Durham	North Carolina	United States
11	Children's Hospital Philadelphia	Philadelphia	Pennsylvania	United States	19104
12	Medical University of South Carolina	Charleston	South Carolina	United States	29403
13	University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75235
14	Texas Transplant Institute	San Antonio	Texas	United States	78229
15	Hopital Ste-Justine	Montreal	Quebec	Canada

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair: Victor Aquino, University of Texas Southwestern Medical Center - Dallas
Study Chair: Nancy Bunin, Children's Hospital of Philadelphia
Study Chair: Martin Champagne, Hopital Ste-Justine
Study Chair: Joel Brochstein, Hackensack Meridian Health
Study Chair: Michael Joyce, Nemours Children's Clinic
Study Chair: Naynesh Kamani, Children's National Research Institute
Study Chair: Gary Kleiner, University of Miami Batchelor Children's Research Center
Study Chair: Joanne Kurtzberg, Duke University Medical Center Children's Hospital
Study Chair: Bertram H. Lubin, UCSF Benioff Children's Hospital Oakland
Study Chair: Alexis Thompson, Ann & Robert H Lurie Children's Hospital of Chicago
Study Chair: Donna Wall, Texas Transplant Institute
Study Chair: Mark Walters, UCSF Benioff Children's Hospital Oakland
Study Chair: Lolie Yu, Louisiana State University Children's Medical Center