NCT01625351

A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 2 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I study designed to determine the feasibility of transplantation using a novel transplant approach that employs a two-stage haploidentical cell infusion following myeloablative conditioning. This strategy, which includes selective depletion of naïve T cells, may speed immune reconstitution thereby potentially reducing the limitations of traditional haploidentical hematopoietic stem cell transplantation (HSCT) and increasing its potential therapeutic application. Additionally, the investigators intend to explore overall survival, event-free survival, hematopoietic cell recovery and engraftment as well as infection rates and complications in these patients.

Detailed description

Twelve participants and 12 donors will be enrolled on this study. Donors will undergo seven days of hematopoietic stem cell (HSC) mobilization followed by two apheresis collections. Each apheresis collection will be processed by the CliniMACS system. DONORS: A mobilization regimen of granulocyte colony stimulating factor (G-CSF) will be used to obtain a peripheral blood stem cell (PBSC) product from the donor. Apheresis will be performed for a minimum of two consecutive days, including one day for each cell product delivered. STUDY PARTICIPANTS: Participants will undergo a two-stage haploidentical cell infusion following myeloablative conditioning. The first cell infusion will be a CD3-depleted product and the second infusion will be a CD45RA-depleted product. Primary Objective: * To determine the feasibility of haploidentical HSCT using two infusions engineered by negative selection on the Miltenyi CliniMACS system- the first by selective depletion of CD3+ cells, followed by a second depleted of CD45RA+ cells, in children with relapsed or refractory solid tumors or lymphomas. Secondary Objectives: * To estimate hematopoietic cell recovery and engraftment rates for the patients. * To estimate infection rates and complications. * To estimate the one-year overall survival (OS) and event-free survival (EFS) for the study patients.

Conditions

• Ewing Sarcoma
• Gastrointestinal Tumor
• Germ Cell Tumor
• Hepatic Tumor
• Lymphoma
• Wilms Tumor
• Rhabdoid Tumor
• Clear Cell Carcinoma
• Renal Cell Carcinoma
• Melanoma
• Neuroblastoma
• Rhabdomyosarcoma
• Non-rhabdomyosarcoma

Interventions

Type	Name	Description
DRUG	alemtuzumab	Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).
DRUG	fludarabine	Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)
DRUG	sirolimus	Patients receive sirolimus beginning on day -1 with taper beginning on day 90. (Day 0 = stem cell transplantation.) Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
DRUG	Busulfan	Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)
DRUG	melphalan	Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)
BIOLOGICAL	stem cells	Patients undergo CD3 depleted haploidentical hematopoietic stem cell transplant (HSCT) on day 0. Patients also undergo CD45RA depleted HSCT infusion on day 1. (Day 0 = stem cell transplantation.)
DEVICE	CliniMACS	The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Timeline

• Start date: 2012-08-20
• Primary completion: 2020-02-10
• Completion: 2020-02-10
• First posted: 2012-06-21
• Last updated: 2026-02-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study