Cord Blood Transplantation for Sickle Cell Anemia and Thalassemia

NCT00029380 | Completed Phase 2

• 2 other identifiers: 141U01HL061877
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 15

Brief Summary

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

Conditions

Hematologic Diseases; Anemia, Sickle Cell; Beta-Thalassemia; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (2)

• Hematologic parameters

• GVHD

Interventions

Sangstat DRUG

Cyclophosphamide DRUG

Busulfan DRUG

Mycophenolate Mofetil DRUG

Cyclosporine DRUG

Cord Blood Transplantation PROCEDURE

Eligibility Criteria

• Age: 3 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (15)

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's Hospital, Oakland

Oakland, California, 94609, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Batchelor Children's Research Center

Miami, Florida, 33136, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Louisiana State University Children's Medical Center

New Orleans, Louisiana, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Duke University Medical Center Children's Hospital

Durham, North Carolina, United States

Location

Children's Hospital Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75235, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Hopital Ste-Justine

Montreal, Quebec, Canada

Location

Related Publications (7)

• 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.

  PMID: 11132238 BACKGROUND

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

  PMID: 10645470 BACKGROUND

• 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.

  PMID: 12430622 BACKGROUND

• 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.

  PMID: 12393579 BACKGROUND

• 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.

  PMID: 12424197 BACKGROUND

• 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.

  PMID: 12673840 BACKGROUND

• Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

  PMID: 36240296 DERIVED

MeSH Terms

Conditions

Hematologic Diseases; Anemia, Sickle Cell; beta-Thalassemia

Interventions

Cyclophosphamide; Busulfan; Mycophenolic Acid; Cyclosporine; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 10, 2002
• First Posted: January 11, 2002
• Study Start: January 1, 1999
• Primary Completion: August 1, 2006
• Study Completion: August 1, 2006
• Last Updated: July 29, 2016

Record last verified: 2008-09

Locations

CA (1); US (14)