Chemotherapy With CD133+ Select Autologous Hematopoietic Stem Cells for Children With Solid Tumors and Lymphomas

Sponsor

St. Jude Children's Research Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00152126

Collaborator

University of Miami (Other)

Enrollment

Location

Arm

66.1

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Studies have provided evidence that residual microscopic malignant cells in autologous bone marrow or blood stem cell grafts can contribute to posttransplant relapse. Researchers are currently exploring different methods in an attempt to purify or "purge" the stem cell product to minimize the risk of tumor contamination.

The CD133+ antigen is a protein contained on or "expressed" on numerous cells in the human body including specific hematopoietic progenitor (blood forming) cells. However, this antigen is not expressed on certain cancer cells including neuroblastoma. A technique using the investigational CliniMACS cell sorting device has been developed in an effort to filter out only those stem cells that express this CD133+ antigen in order to infuse a hematopoietic stem cell product with no tumor contamination potential.

The primary objective of this study is to establish safety of treating patients with a high dose chemotherapy regimen of Busulfan and Melphalan followed by autologous CD133+ hematopoietic stem cell support. Transplants recipients are expected to achieve engraftment as defined by an absolute neutrophil count of greater than or equal to 500/mm3 for three consecutive days by day 42-post infusion. Thus, safety of the treatment plan will be evaluated in terms of failure to engraft by this specific time period.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma Central Nervous System Tumors Lymphomas Wilms Tumor	Procedure: Stem Cell Transplantation Drug: Busulfan, Melphalan	N/A

Detailed Description

Secondary objectives for this protocol include the following:

To describe CD133+ graft content post-selection and to describe the yield and purity of CD133+ content of the graft obtained.
To describe the negative selection efficiency of this strategy by assessing the processed product for tumor specific markers, when applicable.
To characterize the proliferation of clonal progeny of CD133+ cells.
To characterize lymphocyte and hematopoietic reconstitution (including the kinetics of platelet engraftment) in these patients.
To estimate one-year disease-free and overall survival in these transplant recipients.

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Busulfan and Melphalan With Autologous Hematopoietic Stem Cell Support With Positively-Selected CD133+ Hematopoietic Cells for Children With High Risk Solid Tumors and Lymphomas

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

Aug 1, 2005

Actual Study Completion Date :

Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: 1	Procedure: Stem Cell Transplantation Autologous stem cell transplantation Drug: Busulfan, Melphalan Transplant recipients will receive high dose Busulfan and Melphalan followed by autologous CD133+ antigen specific hematopoietic stem cell infusion. The autologous graft product will be selected using the investigational CliniMACS device. Other Names: Autologous stem cell transplant CD133+ antigen specific selection Apheresis

Arm

Intervention/Treatment

Other: 1

Procedure: Stem Cell Transplantation

Autologous stem cell transplantation

Drug: Busulfan, Melphalan

Transplant recipients will receive high dose Busulfan and Melphalan followed by autologous CD133+ antigen specific hematopoietic stem cell infusion. The autologous graft product will be selected using the investigational CliniMACS device.

Other Names:

Autologous stem cell transplant

CD133+ antigen specific selection

Apheresis

Outcome Measures

Primary Outcome Measures

To determine the safety of the treatment plan using Busulfan and Melphalan followed by infusion of CD133+ selected hematopoietic cells in patients with high-risk malignancies. [August 2005]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligibility will be determined separately for Part I and Part II of this study:

Part I ( Part I Eligibility criteria (eligibility for undergoing apheresis procedure)

Age ≤ 25 years at initial diagnosis.
Must have one of the following diagnoses:
High risk neuroblastoma
Metastatic or recurrent retinoblastoma
High risk rain tumors
Recurrent or refractory Hodgkin disease
Recurrent or advanced stage Wilms tumor
Recurrent or metastatic sarcomas
Recurrent or refractory non-Hodgkin lymphoma
Desmoplastic small round cell tumor.
Lansky or Karnofsky Performance Score ≥ 70.
Creatinine ≤ 2.0 mg/dl.
Direct bilirubin ≤ 2.0 mg/dl.
SGPT ≤ 2 x upper limit of normal
HIV testing
Negative pregnancy test
Patients with significant prior radiation therapy to the liver will be excluded.

Part II eligibility criteria (criteria for transplantation of CD133 select stem cell product)

Successfully completed Part I of protocol treatment plan and has the following available:
Stored autologous bone marrow or peripheral blood stem cells (i.e. 2 x 106 unselected CD34+ cells/ kg PBSC or 1 x 106 CD34+ cells/ kg BM) for back up.
Stored autologous bone marrow or peripheral blood stem cells (2 x 106 CD133+ cells/ kg PBSC or 2 x 106 CD133+ cells/ kg BM) for infusion.
Forced vital capacity greater than or equal to 40% normal or pulse oximetry greater than or equal to 92% on room air.
Lansky or Karnofsky Performance Score ≥ 70.
Creatinine ≤ 2.0 mg/dl.
Direct bilirubin ≤ 2.0 mg/dl.
SGPT ≤ 2 x upper limit of normal
Negative pregnancy test
Patients with significant prior radiation therapy (in opinion of the PI) to the liver will be excluded.