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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01279616
Recruitment Status : Terminated (PI moving to a different institution.)
First Posted : January 19, 2011
Results First Posted : April 3, 2019
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Nationwide Children's Hospital

Tracking Information
First Submitted Date  ICMJE January 18, 2011
First Posted Date  ICMJE January 19, 2011
Results First Submitted Date  ICMJE February 21, 2019
Results First Posted Date  ICMJE April 3, 2019
Last Update Posted Date April 3, 2019
Actual Study Start Date  ICMJE September 2010
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
Event-free Survival [ Time Frame: 1 year ]
Event-free survival
Original Primary Outcome Measures  ICMJE
 (submitted: January 18, 2011)
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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2011)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease
Official Title  ICMJE A Pilot Study of an Immunosuppressive and Myeloablative Preparative Regimen for Allogeneic Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Severe Sickle Cell Disease
Brief Summary 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.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • 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 microM.mt
    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
Study Arms  ICMJE Experimental: Hematopoietic Stem Cell Transplant
Stem cell infusion on Day 0.
Interventions:
  • Drug: Fludarabine monophosphate
  • Drug: Rituximab
  • Drug: Busulfan
  • Drug: ATG
  • Drug: Cyclophosphamide
  • Drug: Mycophenolate mofetil
  • Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 2, 2019)
8
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2011)
25
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01279616
Other Study ID Numbers  ICMJE 09-00383
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nationwide Children's Hospital
Study Sponsor  ICMJE Nationwide Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Sandeep Soni, MD Nationwide Children's Hospital
PRS Account Nationwide Children's Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP