Status:

COMPLETED

Sickle Cell Disease Conditioning for Bone Marrow Transplant

Lead Sponsor:

Emory University

Conditions:

Bone Marrow Transplantation

Sickle Cell Disease

Eligibility:

All Genders

Up to 18 years

Phase:

PHASE1

Brief Summary

Most bone marrow transplants for children with sickle cell disease are performed using high doses of two chemotherapy agents: busulfan and cyclophosphamide for the pre-transplant conditioning. This ap...

Detailed Description

Many children with sickle cell disease are severely affected by acute complications, especially stroke, recurrent and debilitating pain, or recurrent acute chest syndrome. As they become adolescents a...

Eligibility Criteria

Inclusion

  • Up to and including the age of 18 years at time of admission for transplant
  • Hemoglobin SS, or hemoglobin S0 thalassemia
  • HLA-identical sibling donor (any age) available without HgbSS, SC or S0 thalassemia. As an alternative, HLA identical sibling umbilical cord blood can be used as long as the unit has a pre-cryopreservation TNC dose of greater than 5.0 x 107 TNC/kg recipient weight.
  • Clinically severe SCD, defined by one of the following:
  • Previous clinical stroke, as evidenced by a neurological deficit lasting longer than 24 hours, which is accompanied by radiographic evidence of ischemic brain injury and cerebral vasculopathy.
  • Asymptomatic cerebrovascular disease, as evidenced by one the following:
  • (i)Progressive silent cerebral infarction, as evidenced by serial MRI scans that demonstrate the development of a succession of lesions (at least two temporally discreet lesions, each measuring at least 3 mm in greatest dimension on the most recent scan) or the enlargement of a single lesion, initially measuring at least 3 mm). Lesions must be visible on T2-weighted MRI sequences.
  • (ii) Cerebral arteriopathy, as evidenced by abnormal TCD testing (confirmed elevated velocities in any single vessel of TAMMV \> 200 cm/sec for non-imaging TCD or TAMX \> 185 cm/sec for imaging TCD) or by significant vasculopathy on MRA (greater than 50% stenosis of \> 2 arterial segments or complete occlusion of any single arterial segment).
  • (c) Frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes (defined as episode lasting ≥ 4 hours and requiring hospitalization or outpatient treatment with parenteral opioids). If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 2 years prior to the start of this drug.
  • (d) Recurrent (≥ 3 in lifetime) acute chest syndrome events that have necessitated erythrocyte transfusion therapy.
  • (e) Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 3 years prior to the start of this drug.
  • Must have been evaluated and adequately counseled regarding treatment options for severe sickle cell disease by a pediatric hematologist.

Exclusion

  • Biopsy proven chronic active hepatitis, portal fibrosis (greater than score I), or cirrhosis, or serologic evidence of active hepatitis.
  • SCD chronic lung disease stage III (see appendix 1).
  • Severe renal dysfunction defined as \< 50% of predicted normal GFR for age.
  • Severe cardiac dysfunction defined as shortening fraction \< 25%.
  • Severe residual neurologic impairment other than hemiplegia alone, defined as full-scale IQ 70, quadriplegia or paraplegia, inability to ambulate, inability to communicate without assistive device, or any impairment resulting in decline of Lansky performance score to \< 70%.
  • CNS event occurring within 6 months prior to transplant.
  • Karnofsky or Lansky functional performance score \< 70%.
  • Confirmed HIV seropositivity.
  • Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
  • Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
  • History of lack of compliance with medical care that would jeopardize transplant course.
  • Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia.
  • Donor is HIV infected.
  • Donor is pregnant.

Key Trial Info

Start Date :

February 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 11 2016

Estimated Enrollment :

8 Patients enrolled

Trial Details

Trial ID

NCT00968162

Start Date

February 1 2009

End Date

January 11 2016

Last Update

July 25 2017

Active Locations (10)

Enter a location and click search to find clinical trials sorted by distance.

Page 1 of 3 (10 locations)

1

University of Alabama-Birmingham

Birmingham, Alabama, United States

2

Children's National Medical Center

Washington D.C., District of Columbia, United States

3

All Children's Research Institute Inc.

St. Petersburg, Florida, United States, 33701

4

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30322