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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00244010
First received: October 24, 2005
Last updated: May 1, 2012
Last verified: February 2009
  Purpose

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.


Condition Intervention
Anemia, Aplastic
Amegakaryocytic Thrombocytopenia
Diamond-Blackfan Anemia
Kostmann Syndrome
Device: Allogeneic stem cell transplant

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplantation (HSCT) From Partially Matched Family Donors for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias: A Pilot Study

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Treatment Failures [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 4
Study Start Date: October 2005
Study Completion Date: February 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 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

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.
  Eligibility

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

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
  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: NCT00244010

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Kimberly Kasow, DO St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00244010     History of Changes
Other Study ID Numbers: SAAHAP, Severe Aplastic Anemia, Cytopenias
Study First Received: October 24, 2005
Results First Received: February 2, 2012
Last Updated: May 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Aplastic anemia
Amegakaryocytic thrombocytopenia
Diamond-Blackfan Anemia
Kostmann syndrome
Allogeneic stem cell transplantation
Haploidentical stem cell transplant
T-cell depletion
Partially matched family member donor transplant
Refractory cytopenia

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Anemia, Diamond-Blackfan
Anemia, Hypoplastic, Congenital
Syndrome
Thrombocytopenia
Neutropenia
Hematologic Diseases
Disease
Pathologic Processes
Blood Platelet Disorders
Bone Marrow Diseases
Red-Cell Aplasia, Pure
Genetic Diseases, Inborn
Agranulocytosis
Leukopenia
Leukocyte Disorders

ClinicalTrials.gov processed this record on October 16, 2014