Stem Cell Transplant in Sickle Cell Disease and Thalassemia

Sickle Cell Disease Clinical Trial

Official title:

Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00408447
• Other study ID #: AAAA7701
• Secondary ID: CHNY-01-503
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 2004
• Est. completion date: December 2023

Study information

• Verified date: March 2023
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Beta Thalassemia
• beta-Thalassemia
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• Busulfan
Busulfan 4 mg/kg/d x 4d
• Fludarabine
Fludarabine 30 mg/m2/d x 6d
• Alemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d

Procedure:
• 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.

Locations

Country	Name	City	State
United States	Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.	days 60, 100, 180, 365, 730
Secondary	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	To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.	as clinically appropriate
Secondary	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	To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.	6mos, 1 yr, 2 yr
Secondary	Quality of life (QOL) score	To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time	Day +180; year 1, 3, 5, 10
Secondary	Incidence of primary and secondary graft failure	To collect data on graft failure	Day +42, +60,
Secondary	Percent of mixed donor chimerism	To collect data on donor chimerism	Day +30, 60, 100, 180, 365, 730, and 1005