Trials / Completed

CompletedNCT00566696

Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies

A Reduced Intensity Conditioning Regimen With CD3-Depleted Hematopoietic Stem Cells to Improve Survival for Patients With Hematologic Malignancies Undergoing Haploidentical Stem Cell Transplantation

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 73 (actual)

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

Summary

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including 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 body tissues of the patient (the host) 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 significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

Detailed description

This study will explore the following objectives: 1. To assess if the event-free survival at one-year post-transplant for research participants with high-risk hematologic malignancies can be improved following HAPLO hematopoietic stem cell transplant (HSCT) using a graft depleted of CD3+ cells ex vivo and a reduced intensity-conditioning regimen. Secondary objectives: 1. To estimate the one-year overall survival (OS) and disease-free survival (DFS) for research participants who receive this study treatment. 2. To estimate the cumulative incidence of relapse for research participants who receive this study treatment. 3. To estimate the rate of overall grade III-IV acute GVHD, and the rate and severity of chronic GVHD in research participants. 4. To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant. Exploratory objectives: 1. To explore the biologic significance of soluble interleukin-2 receptor and immunologic state \[quantitative lymphocyte studies, V beta spectratyping, T-cell receptor excision circles (TREC) assay\] to predict the development of acute and chronic GVHD in these research participants. 2. To measure the pharmacokinetics of Campath-1H in pediatric HAPLO HSCT recipients NOTE: This protocol originally used muromonab (OKT3) in the conditioning regimen to prepare participants for haploidentical HCT. After muromonab became unavailable from the manufacturer in 2010, muromonab was replaced by alemtuzumab (Campath-1H) for use in subsequent participants.

Conditions

Interventions

Type	Name	Description
DEVICE	CliniMACS	Miltenyi Biotec CliniMACS stem cell selection device
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.
DRUG	Fludarabine	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Thioplex®	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	L-phenylalanine mustard	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Mycophenolate mofetil	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Rituxan™	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Alemtuzumab	After January 2010, due to the unavailability of muromonab, transplant recipients received a conditioning regimen consisting of systemic chemotherapy and antibodies, including alemtuzumab.
DRUG	Cyclophosphamide	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Anti-thymocyte globulin (Rabbit)	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	G-CSF	Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.
DRUG	Muromonab	Prior to January 2010, transplant participants received a conditioning regimen consisting of systemic chemotherapy and antibodies, including muromonab. Muromonab became unavailable from the manufacturer at that time and was replaced by alemtuzumab.

Timeline

Start date: 2007-12-14
Primary completion: 2016-01-27
Completion: 2020-02-06
First posted: 2007-12-03
Last updated: 2020-04-14
Results posted: 2016-05-03

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00566696. Inclusion in this directory is not an endorsement.