Stem Cell Transplant in Sickle Cell Disease and Thalassemia

Phase 2

Active, not recruiting

• Conditions: Sickle Cell Disease; Beta Thalassemia
• Interventions: Drug: Busulfan; Drug: Fludarabine; Drug: Alemtuzumab; Procedure: Allogeneic stem cell transplant

• Registration Number: NCT00408447
• Lead Sponsor: Columbia University

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).

Study Timeline

• Study Start: 2004-09
• Study First Submitted: 2006-12-06
• Study First Submitted QC: 2006-12-06
• Study First Posted: 2006-12-07
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-11
• Last Update Posted: 2024-06-13
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 53

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SCD group	Fludarabine	Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
SCD group	Alemtuzumab	Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
SCD group	Allogeneic stem cell transplant	Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
BT group	Busulfan	Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
BT group	Fludarabine	Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
BT group	Alemtuzumab	Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
BT group	Allogeneic stem cell transplant	Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
SCD group	Busulfan	Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Primary Outcome Measures

Name	Time	Method
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)	Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years	To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.

Secondary Outcome Measures

Name	Time	Method
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	To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.
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	To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.
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	To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.
Quality of life (QOL) score	Day +180; year 1, 3, 5, 10	To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time
Incidence of primary and secondary graft failure	Day +42, +60,	To collect data on graft failure
Percent of mixed donor chimerism	Day +30, 60, 100, 180, 365, 730, and 1005	To collect data on donor chimerism

Trial Locations

Locations (1)

Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University; 🇺🇸 New York, New York, United States