Cord Blood Transplantation for Sickle Cell Anemia and Thalassemia

• ClinicalTrials.gov Identifier: NCT00029380
• Recruitment Status: Completed
• First Posted: January 11, 2002
• Last Update Posted: July 29, 2016
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by: National Heart, Lung, and Blood Institute (NHLBI)

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 (Clinical Trial)
• Estimated Enrollment: 30 participants
• Primary Purpose: Treatment
• Official Title: Sibling Donor Cord Blood Banking and Transplantation
• Study Start Date: January 1999
• Actual Primary Completion Date: August 2006
• Actual Study Completion Date: August 2006

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Hematologic parameters
2. GVHD

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 14 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

  1. 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.
  2. 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
  3. Any combination of painful events and episodes of ACS that total three events in the 2 years before transplantation
  4. Any clinically significant neurologic event (stroke or hemorrhage) or any neurologic defect lasting more than 24 hours
  5. Abnormal cerebral MRI and abnormal cerebral MRA
  6. 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)
  7. 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:

  1. 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%
  2. 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)
  3. 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
  4. 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

United States, California

Children's Hospital Oakland

Oakland, California, United States, 94609

Children's Hospital, Oakland

Oakland, California, United States, 94609

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States

United States, Florida

Nemours Children's Clinic

Jacksonville, Florida, United States, 32207

University of Miami Batchelor Children's Research Center

Miami, Florida, United States, 33136

United States, Illinois

Children's Memorial Hospital

Chicago, Illinois, United States, 60614

United States, Louisiana

Louisiana State University Children's Medical Center

New Orleans, Louisiana, United States

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, North Carolina

Duke University Medical Center Children's Hospital

Durham, North Carolina, United States

United States, Pennsylvania

Children's Hospital Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29403

United States, Texas

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States, 75235

Texas Transplant Institute

San Antonio, Texas, United States, 78229

Canada, Quebec

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

More Information

Publications:

Reed W, Walters M, Lubin BH. Collection of sibling donor cord blood for children with thalassemia. J Pediatr Hematol Oncol. 2000 Nov-Dec;22(6):602-4. doi: 10.1097/00043426-200011000-00031.

Lubin BH, Eraklis M, Apicelli G. Umbilical cord blood banking. Adv Pediatr. 1999;46:383-408. No abstract available.

Woodard P, Lubin B, Walters CM. New approaches to hematopoietic cell transplantation for hematological diseases in children. Pediatr Clin North Am. 2002 Oct;49(5):989-1007. doi: 10.1016/s0031-3955(02)00026-3.

Reed W, Smith R, Dekovic F, Lee JY, Saba JD, Trachtenberg E, Epstein J, Haaz S, Walters MC, Lubin BH. Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease. Blood. 2003 Jan 1;101(1):351-7. doi: 10.1182/blood-2002-02-0394. Epub 2002 Aug 8.

Locatelli F, Rocha V, Reed W, Bernaudin F, Ertem M, Grafakos S, Brichard B, Li X, Nagler A, Giorgiani G, Haut PR, Brochstein JA, Nugent DJ, Blatt J, Woodard P, Kurtzberg J, Rubin CM, Miniero R, Lutz P, Raja T, Roberts I, Will AM, Yaniv I, Vermylen C, Tannoia N, Garnier F, Ionescu I, Walters MC, Lubin BH, Gluckman E; Eurocord Transplant Group. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood. 2003 Mar 15;101(6):2137-43. doi: 10.1182/blood-2002-07-2090. Epub 2002 Nov 7.

Reed W, Walters M, Trachtenberg E, Smith R, Lubin BH. Sibling donor cord blood banking for children with sickle cell disease. Pediatr Pathol Mol Med. 2001 Mar-Apr;20(2):167-74.

• Responsible Party: Bertram H. Lubin, Children's Hospital, Oakland
• ClinicalTrials.gov Identifier: NCT00029380
• Other Study ID Numbers: 141; U01HL061877 ( U.S. NIH Grant/Contract )
• First Posted: January 11, 2002
• Last Update Posted: July 29, 2016
• Last Verified: September 2008

Additional relevant MeSH terms:

Anemia; Thalassemia; Hematologic Diseases; beta-Thalassemia; Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Genetic Diseases, Inborn; Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Busulfan; Cyclosporins; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Enzyme Inhibitors; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Calcineurin Inhibitors; Antibiotics, Antineoplastic; Antibiotics, Antitubercular