Stem Cell Transplant in Sickle Cell Disease and Thalassemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Columbia University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00408447
First received: December 6, 2006
Last updated: October 14, 2011
Last verified: October 2011
  Purpose

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).

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.


Condition Intervention Phase
Sickle Cell Disease
Beta Thalassemia
Drug: Busulfan
Drug: Fludarabine
Drug: Alemtuzumab
Procedure: Allogeneic stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • To determine the toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with sickle cell disease and Beta thalassemia [ Time Frame: Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the time to donor hematological reconstitution (neutrophil, RBC and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT [ Time Frame: days 30, 60, 100, 180, 365 ] [ Designated as safety issue: No ]
  • to estimate the 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 [ Time Frame: as clinically appropriate ] [ Designated as safety issue: No ]
  • to determine the 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 [ Time Frame: 6mos, 1 yr, 2 yr ] [ Designated as safety issue: No ]
  • to determine the impact of moderately ablative stem cell transplant on quality of life (QOL) and on neurocognitive functioning of patients with SCD and BT over time. [ Time Frame: Day +180; year 1, 3, 5, 10 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2001
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
SCD group
Sickle Cell Disease
Drug: Busulfan
Busulfan 4 mg/kg/d x 4d
Other Name: Busulfex
Drug: Fludarabine
Fludarabine 30 mg/m2/d x 6d
Other Name: Fludara
Drug: Alemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
Other Name: Campath
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.
Other Names:
  • Related Bone Marrow
  • Related Cord Blood
BT group
Beta Thalassemia
Drug: Busulfan
Busulfan 4 mg/kg/d x 4d
Other Name: Busulfex
Drug: Fludarabine
Fludarabine 30 mg/m2/d x 6d
Other Name: Fludara
Drug: Alemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
Other Name: Campath
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.
Other Names:
  • Related Bone Marrow
  • Related Cord Blood

Detailed Description:

Further study details will be provided by Columbia University, Division of Pediatric Blood & Marrow Transplantation.

STUDY DESIGN:

Patients will receive busulfan, fludarabine and alemtuzumab prior to the stem cell transplant to help the stem cells take and grow. The stem cells will be infused on day 0 through an intravenous catheter. Patients will receive immunosuppressive therapy such as tacrolimus and MMF to prevent graft-versus-disease.

Patients will be followed up after transplant to look for special cells in the blood that show that the new bone marrow is taking hold (engrafting). Response shall be documented at 6 months, 1 year, 2 years and 3 years post-SCT.

  Eligibility

Ages Eligible for Study:   1 Month to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Sickle Cell Disease:

  • Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin SC or SB/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with HgB < 10 or equal to 10 mg/dL
  • Age < or equal to 21
  • Matched sibling donor and asymptomatic

Thalassemia:

Homozygous B-thalassemia

Clinical syndrome of B-thalassemia intermedia (including double heterozygotes, e.g. Hgb E-Beta thalassemia) who either:

  • Require regular transfusions, or
  • Have evidence of severe ineffective erythropoiesis - marked marrow hyperplasia and the resultant cosmetic abnormalities and/or retardation of growth and development as a result of severe anemia.

and:

  • Lucarelli Stage 1 or 2
  • Age < or equal to 21

Additionally,

Patient must have adequate organ function as below:

  • Adequate renal function defined as serum creatinine < or equal to 1.5 x normal, or creatinine clearance or radioisotope GFR =40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
  • Adequate liver function defined as SGOT (AST) or SGPT (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 uncorrected DLCO≥35% by pulmonary function test; for children who are uncooperative, no evidence of dyspnea at rest

Exclusion Criteria

  • Karnofsky/Lansky Performance Score <60%
  • Demonstrated lack of compliance with medical care
  • Pregnant or nursing
  • Sickle Cell Disease: Grade III-IV* residual non-motor neurologic; Grade IV* Hematuria
  • Thalassemia: Lucarelli Stage 3
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00408447

Contacts
Contact: Monica Bhatia, MD 212 305 9138 mb2476@columbia.edu

Locations
United States, New York
Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University Recruiting
New York, New York, United States, 10032
Contact: Monica Bhatia, MD    212-305-9138    mb2476@columbia.edu   
Principal Investigator: Monica Bhatia, MD         
Sponsors and Collaborators
Columbia University
  More Information

Additional Information:
Publications:
Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00408447     History of Changes
Other Study ID Numbers: AAAA7701, CHNY-01-503
Study First Received: December 6, 2006
Last Updated: October 14, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
stem cell transplant
sickle cell disease
thalassemia
moderately ablative
cord blood transplant
matched family donor

Additional relevant MeSH terms:
Beta-Thalassemia
Anemia, Sickle Cell
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Busulfan
Fludarabine phosphate
Fludarabine
Alemtuzumab
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 21, 2014