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

Phase 1

Completed

• Conditions: Lymphoma; Renal Cell Carcinoma; Gastrointestinal Tumor; Hepatic Tumor; Wilms Tumor; Clear Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma
• Interventions: Drug: alemtuzumab; Drug: fludarabine; Drug: sirolimus; Drug: Busulfan; Drug: melphalan; Biological: stem cells; Device: CliniMACS

• Registration Number: NCT01625351
• Lead Sponsor: St. Jude Children's Research Hospital

Brief 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.

Study Timeline

• Study First Submitted: 2012-06-19
• Study First Submitted QC: 2012-06-20
• Study First Posted: 2012-06-21
• Study Start: 2012-08-20
• Primary Completion: 2020-02-10
• Study Completion: 2020-02-10
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-14
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	alemtuzumab	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	fludarabine	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	stem cells	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	CliniMACS	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	Busulfan	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	sirolimus	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.
Treatment	melphalan	Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells. 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. Cells for infusion are prepared using the CliniMACS System.

Primary Outcome Measures

Name	Time	Method
Feasibility of haploidentical HSCT	30 days post transplantation	Feasibility is defined as engraftment (ANC≥ 500/mm3 for 3 consecutive tests performed on different days) evaluated before day +30.

Secondary Outcome Measures

Name	Time	Method
hematopoietic cell recovery and engraftment rates	30 days post transplantation	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.
overall survival (OS)	up to 1 year after transplantation	Defined based on any death. The Kaplan-Meier Estimate will be provided.
event-free survival	up to 1 year after transplantation	The Kaplan-Meier Estimate will be provided.
infection rates and complications	up to 5 years	The proportion of patients who develop infections and complications will be estimated and a Blyth-Still-Casella 95% confidence interval will be provided.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States