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

NCT00244010 | Completed Results

• 3 other identifiers: SAAHAPSevere Aplastic AnemiaCytopenias
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia, Aplastic; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Kostmann Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Treatment Failures

  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.

  100 days post transplant

Study Arms (1)

1

OTHER

Device: Allogeneic stem cell transplant

Interventions

Allogeneic stem cell transplant DEVICE

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.

Also known as: Allogeneic stem cell transplantation, Haploidentical stem cell transplant, T-cell depletion, Partially matched family member donor transplant, Hematopoietic stem cell transplant

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Anemia, Aplastic; Anemia, Diamond-Blackfan; Neutropenia, Severe Congenital, Autosomal Recessive 3; Cytopenia

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Hypoplastic, Congenital; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

This study has terminated due to the PI leaving the institution. An insufficient number of subjects were enrolled to answer the primary objective.

Results Point of Contact

• Title: Kimberly Kasow, DO
• Organization: St. Jude Children's Research Hospital

kimberly_kasow@med.unc.edu

901-595-3300

Study Officials

• Kimberly Kasow, DO

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2005
• First Posted: October 25, 2005
• Study Start: October 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: February 1, 2009
• Last Updated: May 30, 2017
• Results First Posted: May 2, 2012

Record last verified: 2009-02

Locations

US (1)