Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Memphis, Tennessee 38105


Purpose:

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 summary:

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.


Criteria:

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 is Available At:


Original ID:

REFSCT


NCT ID:

NCT00145613


Secondary ID:


Study Acronym:


Brief Title:

Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies


Official Title:

Haploidentical Stem Cell Transplantation Utilizing T-Cell Depletion as Therapy for Patients With Refractory Hematological Malignancies


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

2 Years


Maximum Age:

21 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

St. Jude Children's Research Hospital


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

25


Enrollment Type:

Actual


Overall Contact Information

Official Name:Gregory Hale, M.D.
Principal Investigator
St. Jude Children's Research Hospital

Study Dates

Start Date:June 2003
Completion Date:February 2009
Completion Type:Actual
Primary Completion Date:July 2006
Primary Completion Type:Actual
Verification Date:February 2009
Last Changed Date:February 12, 2009
First Received Date:September 1, 2005

Study Outcomes

Outcome Type:Primary Outcome
Measure: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
Safety Issues:True

Study Interventions

Intervention Type:Procedure
Name:Stem Cell Transplantation
Description:An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Arm Name:1
Intervention Type:Device
Name:Miltenyi Biotec CliniMACS
Description:stem cell selection device
Arm Name:1
Intervention Type:Drug
Name:Systemic chemotherapy and antibodies
Description: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.
Arm Name:1
Other Name:Allogeneic stem cell transplant,

Study Arms

Study Arm Type:Other
Arm Name:1

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:St. Jude Children's Research Hospital

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.