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A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease

This study has been terminated.
(PI moving to a different institution.)
Information provided by (Responsible Party):
Nationwide Children's Hospital Identifier:
First received: January 18, 2011
Last updated: February 2, 2017
Last verified: February 2017
Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell disease lack a matched family donor. This study aims for cure of sickle cell disease by performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood units will be selected from the NMDP database. It is designed to estimate the safety of a novel reduced toxicity, yet an immunosuppressive and myeloablative preparative regimen. This is meant for patients <21 years old who have severe complications from sickle cell and do not have matched sibling donors in the family to undergo stem cell transplant. Patients will undergo transplant using unrelated donor stem cells after receiving the protocol therapy. They will be followed for 1 year to monitor for engraftment of donor cells and complications like graft versus host disease (GVHD), infections and death.

Condition Intervention Phase
Sickle Cell Disease
Drug: Fludarabine monophosphate
Drug: Rituximab
Drug: Busulfan
Drug: ATG
Drug: Cyclophosphamide
Drug: Mycophenolate mofetil
Drug: Tacrolimus
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Pilot Study of an Immunosuppressive and Myeloablative Preparative Regimen for Allogeneic Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Severe Sickle Cell Disease

Resource links provided by NLM:

Further study details as provided by Nationwide Children's Hospital:

Primary Outcome Measures:
  • Event free survival [ Time Frame: 1 year ]
    To determine event free survival (EFS) at 1 year post unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) in pediatric patients < 21 years of age with severe sickle cell disease (SCD) after conditioning with an immunosuppressive and myeloablative conditioning regimen. Death, graft rejection and disease recurrence are the 'evaluable events' considered for this end-point

Secondary Outcome Measures:
  • feasibility and toxicity of preparative regimen [ Time Frame: 1 year ]
    evaluation of feasibility and toxicity of the preparative regimen and the effect of HSCT on the clinical and laboratory manifestations of sickle cell anemia at 1 year post-HSCT

Enrollment: 4
Study Start Date: September 2010
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic Stem Cell Transplant
Stem cell infusion on Day 0.
Drug: Fludarabine monophosphate
180 mg/m2 over 6 days.
Drug: Rituximab
375 mg/m2 on day -13 and day -3
Other Name: Rituxan
Drug: Busulfan
AUC 1000-1200
Other Name: busulfex
Drug: ATG
2.5 mg/kg for 3 days
Other Name: Thymoglobulin
Drug: Cyclophosphamide
50 mg/kg on day +3
Other Name: Cytoxan
Drug: Mycophenolate mofetil
15 mg/kg q 8 hours
Other Name: MMF, Cell-cept.
Drug: Tacrolimus
0.03 mg/kg /d
Other Name: FK-506

Detailed Description:
The primary goal of this pilot study is to determine the safety and feasibility of the preparative regimen for HSCT using a novel reduced toxicity regimen for stem cell transplant with unrelated donors. Analysis will be geared to confirm if the study regimen, followed by an appropriately HLA-matched unrelated donor (MUD)or unrelated cord blood HSCT, can lead to durable donor engraftment with reasonable toxicity, inhibiting sickle erythropoiesis and limiting disease related organ toxicity in patients who are at high risk for morbidity and mortality associated with sickle cell disease (SCD).

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1 or more of the following clinical complications related to Sickle cell disease:

  1. A clinically significant neurologic event (stroke) or any neurologic defect lasting >24 hours, that is accompanied by an infarct on cerebral MRI.
  2. Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least 1 complete lung segment associated with acute symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate supportive care measures (example: asthma therapy, hydroxyurea).
  3. History of severe pain episodes defined as 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures and hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than vaso-occlusion mediated by sickle cell disease.
  4. Recurrent priapism.
  5. Osteo-necrosis of multiple joints
  6. Evidence of Pulmonary Hypertension as evidenced by Tricuspid Regurgitation jet velocity (TRV) > 2.5 m/s on Echocardiogram.
  7. Red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy.

Exclusion Criteria:

  1. Invasive bacterial, viral or fungal infections within 1 month prior to starting conditioning therapy.
  2. Female patients who are Pregnant (Beta HCG +) or breastfeeding.
  3. HIV positive patients.
  4. Patients with HLA-matched related family donors are not eligible for this study.
  5. Prior myeloablative allogeneic HCT.
  6. Patients on chronic transfusion therapy for ≥ 1 year with evidence of cirrhosis of liver on biopsy
  7. Any significant concurrent disease, illness, severe cognitive delay or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
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Please refer to this study by its identifier: NCT01279616

United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Nationwide Children's Hospital
Study Chair: Sandeep Soni, MD Nationwide Children's Hospital
  More Information

Responsible Party: Nationwide Children's Hospital Identifier: NCT01279616     History of Changes
Other Study ID Numbers: 09-00383
Study First Received: January 18, 2011
Last Updated: February 2, 2017

Keywords provided by Nationwide Children's Hospital:
sickle cell
stem cell transplant

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Mycophenolate mofetil
Fludarabine phosphate
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antimetabolites processed this record on April 21, 2017