A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas
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.
Germ Cell Tumor
Clear Cell Carcinoma
Renal Cell Carcinoma
Biological: stem cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas|
- Feasibility of haploidentical HSCT [ Time Frame: 30 days post transplantation ] [ Designated as safety issue: Yes ]Feasibility is defined as engraftment (ANC≥ 500/mm3 for 3 consecutive tests performed on different days) evaluated before day +30.
- hematopoietic cell recovery and engraftment rates [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]They will be reported and presented descriptively. Specifically, the hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.
- infection rates and complications [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]The proportion of patients who develop infections and complications will be estimated and a Blyth-Still-Casella 95% confidence interval will be provided.
- overall survival (OS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]Defined based on any death. The Kaplan-Meier Estimate will be provided.
- event-free survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]The Kaplan-Meier Estimate will be provided.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).
Other Names:Drug: fludarabine
Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)
Other Name: Fludara(R)Drug: sirolimus
Patients receive sirolimus beginning on day -1 with taper beginning on day 90. (Day 0 = stem cell transplantation.)
Other Names:Drug: Busulfan
Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)
Other Names:Drug: melphalan
Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)
Other Names: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.)
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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01625351
|Contact: David R. Shook, MDemail@example.com|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: David R. Shook, MD 866-278-5833 firstname.lastname@example.org|
|Principal Investigator: David R. Shook, MD|
|Principal Investigator:||David R. Shook, MD||St. Jude Children's Research Hospital|