Trials / Completed

CompletedNCT00145613

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

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 25 (actual)

Sponsor: St. Jude Children's Research Hospital · Academic / Other
Sex: All
Age: 2 Years – 21 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

Secondary objectives for this protocol are to 1) assess the kinetics of lymphohematopoietic reconstitution and 2) describe the short and long-term (up to 5 years post- transplant) toxicity of haploidentical stem cell transplantation, including GVHD, in children with refractory hematological malignancies.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Stem Cell Transplantation	An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
DEVICE	Miltenyi Biotec CliniMACS	stem cell selection device
DRUG	Systemic chemotherapy and antibodies	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.

Timeline

Start date: 2003-06-01
Primary completion: 2006-07-01
Completion: 2009-02-01
First posted: 2005-09-05
Last updated: 2009-02-13

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00145613. Inclusion in this directory is not an endorsement.