Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 5 of 17 for:    "Severe Congenital Neutropenia"

Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias

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: NCT00244010
Recruitment Status : Completed
First Posted : October 25, 2005
Results First Posted : May 2, 2012
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date  ICMJE October 24, 2005
First Posted Date  ICMJE October 25, 2005
Results First Submitted Date  ICMJE February 2, 2012
Results First Posted Date  ICMJE May 2, 2012
Last Update Posted Date May 30, 2017
Study Start Date  ICMJE October 2005
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2012)
Treatment Failures [ Time Frame: 100 days post transplant ]
The primary objective of this study is to evaluate the safety of HAPLO HSCT for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can demonstrate that it is associated with a significantly higher treatment failure rate. The treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days post HSCT or after the last cellular product infusion, if required.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2005)
Safety over the first 100 days after transplantation: Absence of grade III-IV (severe) acute graft-versus-host disease, successful donor cell engraftment, survival.
Change History Complete list of historical versions of study NCT00244010 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2005)
  • To examine donor T-cell engraftment for one year after transplantation.
  • 2.To examine donor/host T-regulatory cell populations for one year after transplantation.
  • 3.To monitor rates of acute and chronic graft-versus-host disease for one year after transplantation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
Official Title  ICMJE Hematopoietic Stem Cell Transplantation (HSCT) From Partially Matched Family Donors for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias: A Pilot Study
Brief Summary

Due to an overall and disease free survival of 85% to 100%, allogeneic blood or bone marrow stem cell transplantation using an HLA matched sibling donor is the therapy of choice for patients with severe aplastic anemia (SAA). Unfortunately, only about 25% of patients have such a donor. For patients with SAA lacking a matched sibling donor, immunosuppressive therapy is the current treatment of choice. Approximately 70% of these patients have a complete or partial response to immunosuppressive therapy, achieving transfusion independence and/or growth factor independence.

For the approximately 30% of patients who do not respond to immunosuppressive therapy or experience recurrence, alternative donor (matched unrelated, partially matched family member) transplantation is a treatment option. However, graft rejection and graft-versus-host-disease (GVHD) are significant barriers to success, decreasing event-free survival to 30% to 50%.

This study offers stem cell transplantation using a partially matched family member (haploidentical) donor to those patients with no available HLA-matched sibling or matched unrelated donor. In an attempt to reduce GVHD and regimen-related toxicity while maintaining adequate engraftment, we plan to infuse a highly purified stem cell graft. The Miltenyi Biotec CliniMACS CD3 depletion system will be used to derive a defined allogeneic graft highly enriched for CD34+ hematopoietic cells and depleted of CD3+ T-lymphocytes from G-CSF mobilized, donor-derived peripheral blood stem cells.

Patients 21 years of age and younger with refractory cytopenias are also eligible for this protocol as there are no other potentially curative therapies currently available for these conditions.

The primary objective of this study is to evaluate the safety of transplantation using a haploidentical donor product engineered to targeted cell counts using the investigational CliniMACS device for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can find this type of procedure is associated with a significantly higher treatment failure rate. Treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days after transplant.

Detailed Description

Secondary objectives for this protocol include the following:

  • To observe the degree of hematopoietic chimerism in T-cells during the first year posttransplant.
  • To observe the relative proportions of donor/host T-regulatory cells during the first year posttransplant.
  • To monitor rates of acute and chronic GVHD during the first year posttransplant.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anemia, Aplastic
  • Amegakaryocytic Thrombocytopenia
  • Diamond-Blackfan Anemia
  • Kostmann Syndrome
Intervention  ICMJE Device: Allogeneic stem cell transplant
Participants will receive a reduced intensity conditioning regimen consisting of fludarabine, thiotepa, melphalan, and OKT3 followed by an infusion of haploidentical stem cells. Rituximab will be administered within 24 hours of the infusion in an effort to prevent posttransplant lymphoproliferative disorder LPD. In addition to T-cell depletion of the donor product, participant will receive mycophenolate mofetil for prophylaxis of GVHD.
Other Names:
  • Allogeneic stem cell transplantation
  • Haploidentical stem cell transplant
  • T-cell depletion
  • Partially matched family member donor transplant
  • Hematopoietic stem cell transplant
Study Arms  ICMJE 1
Intervention: Device: Allogeneic stem cell transplant
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 Completed
Actual Enrollment  ICMJE
 (submitted: January 12, 2012)
4
Original Enrollment  ICMJE
 (submitted: October 24, 2005)
14
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • One of the following diagnoses:
  • Refractory severe aplastic anemia
  • Refractory Kostmann syndrome
  • Refractory Diamond-Blackfan anemia
  • Refractory amegakaryocytic thrombocytopenia
  • Absence of a suitable HLA-matched sibling donor and absence of a 10/10 allele matched unrelated donor.
  • Life expectancy of greater than six weeks as per the judgment of the principal investigator.
  • Karnofsky or Lansky Performance Status score of greater than or equal to 70%.
  • Creatinine clearance is greater than or equal to 40 cc/min/1.73 m2.
  • FVC greater than or equal to 40% of predicted or pulse oximetry greater than or equal to 92% on room air.
  • Does not have a known allergy to murine products.

Exclusion criteria:

  • Ejection fraction or shortening fraction below the lower limit of normal for age.
  • Lactating (female patient).
  • Pregnant or lactating
  • Diagnosis of Fanconi Anemia.
  • Positive HLA crossmatch with donor
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 NCT00244010
Other Study ID Numbers  ICMJE SAAHAP
Severe Aplastic Anemia
Cytopenias
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kimberly Kasow, DO St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date February 2009

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