Stem Cell Transplant in Sickle Cell Disease and Thalassemia

NCT00408447 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: AAAA7701CHNY-01-503
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease; Beta Thalassemia

Keywords

stem cell transplant; sickle cell disease; thalassemia; moderately ablative; cord blood transplant; matched family donor

Outcome Measures

Primary Outcomes (1)

• Prevalence of toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with Sickle Cell Disease (SCD) and Beta Thalassemia (BT)

  To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.

  Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years

Secondary Outcomes (6)

• Time to donor hematological reconstitution (neutrophil, red blood cell and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT

  days 60, 100, 180, 365, 730

• Incidence of acute and chronic graft versus host disease (GVHD) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT

  as clinically appropriate

• Percent of patients who have either a complete, very good partial, partial or no response (clinical/laboratory) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT

  6mos, 1 yr, 2 yr

• Quality of life (QOL) score

  Day +180; year 1, 3, 5, 10

• Incidence of primary and secondary graft failure

  Day +42, +60,

Study Arms (2)

SCD group

OTHER

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

Drug: Busulfan; Drug: Fludarabine; Drug: Alemtuzumab; Procedure: Allogeneic stem cell transplant

BT group

OTHER

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

Drug: Busulfan; Drug: Fludarabine; Drug: Alemtuzumab; Procedure: Allogeneic stem cell transplant

Interventions

Busulfan DRUG

Busulfan 4 mg/kg/d x 4d

Also known as: Busulfex

BT group; SCD group

Fludarabine DRUG

Fludarabine 30 mg/m2/d x 6d

Also known as: Fludara

BT group; SCD group

Alemtuzumab DRUG

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

Also known as: Campath

BT group; SCD group

Allogeneic stem cell transplant 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.

Also known as: Related Bone Marrow, Related Cord Blood

BT group; SCD group

Eligibility Criteria

• Age: 1 Month - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

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

New York, New York, 10032, United States

Location

Related Publications (3)

• 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.

  PMID: 15931629 BACKGROUND

• 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.

  PMID: 14730337 BACKGROUND

• 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.

  PMID: 24797180 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia; Thalassemia

Interventions

Busulfan; fludarabine; fludarabine phosphate; Alemtuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Monica Bhatia, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 6, 2006
• First Posted: December 7, 2006
• Study Start: September 1, 2004
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: June 13, 2024

Record last verified: 2024-06

Locations

US (1)