Stem Cell Transplant in Sickle Cell Disease and Thalassemia

NCT ID: NCT00408447

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2025-02-28

Brief Summary

The primary purpose of this study is to see if giving lower doses of chemotherapy (moderately ablative) will result in successful bone marrow replacement without as severe side-effects but with permanent control of the disease. Patients will receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab followed by an infusion of stem cells, either from a family-related or cord-blood matched donor.

Detailed Description

Sickle cell disease is a genetic disorder in which a mutation in the beta chain of human hemoglobin results in abnormal blood hemoglobin, causing red blood cells to sickle under stress with resulting symptoms including severe pains and strokes. Beta thalassemia is another genetic disorder in which there are abnormal beta hemoglobin chains, causing anemia. In both disorders, frequent red blood cell transfusions may be required to sustain life, but these often result in complications including multiple hospitalizations, iron overload, or bacterial or viral infections such as hepatitis. Standard drugs and therapies used in the treatment of sickle cell disease and/or beta thalassemia provide only supportive care, and may result in long-term side effects, and inadequate control of the disease process. Bone marrow transplant has been increasingly used for the long-term treatment and cure of sickle cell disease and beta thalassemia. Although, not without acute and potential long term side effects, this alternative offers long term control and potential cure of the disease. Most of the side effects seen with bone marrow transplant are directly related to the high intensity of chemotherapy used (ablative).

Conditions

Sickle Cell Disease; Beta Thalassemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SCD group

Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Group Type: OTHER

Busulfan

Intervention Type: DRUG

Busulfan 4 mg/kg/d x 4d

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2/d x 6d

Alemtuzumab

Intervention Type: DRUG

Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d

Allogeneic stem cell transplant

Intervention Type: PROCEDURE

Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.

BT group

Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Group Type: OTHER

Busulfan

Intervention Type: DRUG

Busulfan 4 mg/kg/d x 4d

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2/d x 6d

Alemtuzumab

Intervention Type: DRUG

Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d

Allogeneic stem cell transplant

Intervention Type: PROCEDURE

Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.

Interventions

Busulfan

Busulfan 4 mg/kg/d x 4d

Intervention Type: DRUG

Fludarabine

Fludarabine 30 mg/m2/d x 6d

Intervention Type: DRUG

Alemtuzumab

Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d

Intervention Type: DRUG

Allogeneic stem cell transplant

Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.

Intervention Type: PROCEDURE

Other Intervention Names

Busulfex; Fludara; Campath; Related Bone Marrow; Related Cord Blood

Eligibility Criteria

Inclusion Criteria

Sickle Cell Disease:

• Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin Sickle Cell (SC) or S 0/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with hemoglobin (HgB) ≤10 mg/dL
• Age ≤30
• Matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (HLA) matched unrelated adult donor

Patient must have adequate organ function as below:

• Adequate renal function defined as serum creatinine ≤1.5 x normal, or Creatinine clearance or radioisotope glomerular filtration rate (GFR) >100 ml/min/1.73 m2 or >70ml/min/1.73m2 for patients >16 years old
• Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) < 5.0 x normal
• Adequate Cardiac Function defined as shortening fraction of ≥28% by echocardiogram, or ejection fraction of ≥48% by radionuclide angiogram or echocardiogram
• Adequate pulmonary function defined as corrected Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% by pulmonary function test, or for children who are unable to perform DLCO maneuver ≥85% O2 saturation, no evidence of dyspnea at rest

Exclusion Criteria

General

• Karnofsky/Lansky Performance Score <60%
• Demonstrated lack of compliance with medical care
• Pregnant or nursing
• Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.

Histologic Exam of Liver (liver biopsy) with bridging fibrosis or cirrhosis.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Monica Bhatia

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Monica Bhatia, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University

New York, New York, United States

Countries

United States

References

Satwani P, Harrison L, Morris E, Del Toro G, Cairo MS. Reduced-intensity allogeneic stem cell transplantation in adults and children with malignant and nonmalignant diseases: end of the beginning and future challenges. Biol Blood Marrow Transplant. 2005 Jun;11(6):403-22. doi: 10.1016/j.bbmt.2005.04.002.

Reference Type: BACKGROUND

PMID: 15931629 (View on PubMed)

Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid Bradley M, George D, Yamashiro DJ, Garvin J, Skerrett D, Bessmertny O, Wolownik K, Wischhover C, van de Ven C, Cairo MS. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant. 2004 Mar;33(6):613-22. doi: 10.1038/sj.bmt.1704399.

Reference Type: BACKGROUND

PMID: 14730337 (View on PubMed)

Bhatia M, Jin Z, Baker C, Geyer MB, Radhakrishnan K, Morris E, Satwani P, George D, Garvin J, Del Toro G, Zuckerman W, Lee MT, Licursi M, Hawks R, Smilow E, Baxter-Lowe LA, Schwartz J, Cairo MS. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant. 2014 Jul;49(7):913-20. doi: 10.1038/bmt.2014.84. Epub 2014 May 5.

Reference Type: DERIVED

PMID: 24797180 (View on PubMed)

Other Identifiers

CHNY-01-503

Identifier Type: OTHER

Identifier Source: secondary_id

AAAA7701

Identifier Type: -

Identifier Source: org_study_id