Stem Cell Transplant in Sickle Cell Disease and Thalassemia

• Status: Active, not recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Collaborator: Yale University
• Treatments: Alemtuzumab; Busulfan; Fludarabine; Fludarabine phosphate

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.