- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00244010
Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
Hematopoietic Stem Cell Transplantation (HSCT) From Partially Matched Family Donors for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias: A Pilot Study
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Tennessee
-
Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: 1
|
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
100 days post transplant
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SAAHAP
- Severe Aplastic Anemia
- Cytopenias
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Anemia, Aplastic
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingSevere Aplastic Anemia | Idiopathic Aplastic Anemia | Moderate Aplastic Anemia Requiring Transfusions
-
University of UtahNovartisCompletedSevere Aplastic Anemia | Moderate Aplastic Anemia | Very Severe Aplastic AnemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingRecurrent Severe Aplastic Anemia | Refractory Severe Aplastic AnemiaUnited States
-
Peking University People's HospitalRecruiting
-
Boston Children's HospitalNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health... and other collaboratorsRecruitingSevere Aplastic AnemiaUnited States
-
Federal Research Institute of Pediatric Hematology...RecruitingAcquired Aplastic AnemiaRussian Federation
-
Shanghai General Hospital, Shanghai Jiao Tong University...Ruijin Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine and other collaboratorsCompleted
-
Nagoya UniversityUnknownAcquired Aplastic Anemia.Japan
-
Navy General Hospital, BeijingPeking Union Medical College Hospital; Cancer Institute and Hospital, Chinese... and other collaboratorsUnknownSevere Aplastic AnemiaChina
-
Jiangsu HengRui Medicine Co., Ltd.Recruiting
Clinical Trials on Allogeneic stem cell transplant
-
National Cancer Institute (NCI)TerminatedAcute Lymphoblastic Leukemia | Acute Myelogenous Leukemia | Chronic Myelogenous Leukemia | Non-Hodgkins Lymphoma | Hodgkins LymphomaUnited States
-
Center for International Blood and Marrow Transplant...National Marrow Donor ProgramRecruitingMultiple MyelomaUnited States
-
Tata Memorial CentreNot yet recruiting
-
Children's Hospital Medical Center, CincinnatiTerminatedAllogeneic Hematopoietic Cell TransplantationUnited States
-
St. Jude Children's Research HospitalCompletedAcute Myeloid Leukemia | Leukemia | Hodgkin's Lymphoma | Juvenile Myelomonocytic Leukemia | Acute Lymphoblastic Leukemia | Non-Hodgkin Lymphoma | Chronic Myeloid Leukemia | Myelodysplastic Syndrome | Paroxysmal Nocturnal HemoglobinuriaUnited States
-
David Rizzieri, MDCompletedLeukemia | Myelodysplasia | Myeloma | Non Hodgkin's Lymphoma | Hodgkin's DiseaseUnited States
-
Roncarolo, Maria Grazia, MDCalifornia Institute for Regenerative Medicine (CIRM)RecruitingHematologic DiseasesUnited States
-
M.D. Anderson Cancer CenterZiopharm OncologyCompletedLymphoma | LeukemiaUnited States
-
St. Jude Children's Research HospitalCompletedJuvenile Myelomonocytic Leukemia | Non-Hodgkin Lymphoma | Chronic Myeloid Leukemia | Myelodysplastic Syndrome | Acute Lymphoblastic Leukemias | Acute Myelocytic Leukemia | Hemoglobinuria, ParoxysmalUnited States
-
National Cancer Institute (NCI)Active, not recruitingLymphoma, B-Cell | Leukemia, B-cell | Lymphoma, Hodgkins | Lymphoma, Non-hodgkinsUnited States