Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies
Haploidentical Stem Cell Transplantation Utilizing T-Cell Depletion as Therapy for Patients With Refractory Hematological Malignancies
Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple therapies and elevated leukemic/tumor burden usually make these patients ineligible for the aggressive chemotherapy regimens required for conventional stem cell transplantation. Alternative options are needed. One type of treatment being explored is called haploidentical transplant.
Conventional blood or bone marrow stem cell transplant involves destroying the patient's diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused into the patient where it migrates to the bone marrow space to begin generating new blood cells. The best type of donor is a sibling or unrelated donor with an identical immune system (HLA "match"). However, most patients do not have a matched sibling available and/or are unable to identify an acceptable unrelated donor through the registries in a timely manner. In addition, the aggressive treatment required to prepare the body for these types of transplants can be too toxic for these highly pretreated patients. Therefore doctors are investigating haploidentical transplant using stem cells from HLA partially matched family member donors.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD), and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the patient's (the host) body tissues are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for infection. However, the presence of T cells in the graft may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased cells.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution, graft integrity and GVM.
In this study, patients were given a haploidentical graft engineered to with specific T cell parameter values using the CliniMACS system. A reduced intensity, preparative regimen was used to reduce regimen-related toxicity and mortality. The primary goal of this study is to evaluate overall survival in those who receive this study treatment.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria: Refractory hematological malignancies (chemoresistant relapse or primary induction failure) including:
- Acute lymphoblastic leukemia (ALL), must have isolated or combined bone marrow relapse or primary induction failure. Patients with extramedullary relapse are not eligible unless they have previously received a stem cell transplant
- Acute myeloid leukemia (AML) >25% blasts in bone marrow
- Secondary AML
- Myelodysplastic syndrome (MDS)
- Secondary MDS
- Chronic myeloid leukemia (CML)
- Juvenile myelomonocytic leukemia (JMML)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Non-Hodgkin's lymphoma (NHL)*
Hodgkin's Disease (HD)*
*Patients with lymphomas must have failed standard non-cross reactive combination salvage chemotherapy with or without radiation therapy followed by autologous stem cell transplant or patients with chemo resistant disease
- If patient has had previous stem cell transplant, must not be no earlier than 3 months from previous date of transplant
- Patients with shortening fraction greater than or equal to 25%
- Patients with creatinine clearance greater than or equal to 40cc/min/1.73m^2
- Patients with FVC greater than or equal to 40% of predicted, or pulse oximetry greater than or equal to 92% on room air
- Patients with a performance score (Lansky/Karnofsky) of greater than or equal to 50
- Must have a suitable family member donor that is HIV negative, greater than or equal to 18 years of age available for stem cell donation
Exclusion Criteria:
- Patients with a known allergy to murine products
- (Female Patients) Patient is pregnant
- Female Patients) Patient is lactating
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Other: 1
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An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
stem cell selection device
Transplant recipients received a non-TBI based reduced intensity conditioning regimen consisting of OKT-3, Fludarabine Thiotepa, and Melphalan.
Rituximab was administered within 24 hours of the transplant in an effort to prevent PTLPD.
In addition to T-cell depletion of the haploidentical stem cell product, Mycophenolate mofetil was provided as prophylaxis for GVHD.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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To ask in terms of one-year survival the efficacy of haploidentical stem cell transplantation in children with refractory hematological malignancies.
Time Frame: July 2006
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July 2006
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Collaborators and Investigators
Investigators
- Principal Investigator: Gregory Hale, M.D., St. Jude Children's Research Hospital
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 (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Urologic Diseases
- Urological Manifestations
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Urination Disorders
- Anemia
- Neoplastic Processes
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Lymphoid
- Proteinuria
- Anemia, Hemolytic
- Lymphoma
- Neoplasms
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Hodgkin Disease
- Lymphoma, Non-Hodgkin
- Preleukemia
- Leukemia, Myelomonocytic, Juvenile
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Hemoglobinuria
- Hemoglobinuria, Paroxysmal
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
Other Study ID Numbers
- REFSCT
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