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

Neuroblastoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00152126
• Other study ID #: ST133
• Status: Completed
• Phase: N/A
• First received: September 7, 2005
• Last updated: February 12, 2009
• Start date: August 2003
• Est. completion date: February 2009

Study information

• Verified date: February 2009
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2009
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 25 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Lymphoma
• Lymphomas
• Neoplasms
• Nervous System Neoplasms
• Neuroblastoma
• Wilms Tumor

Intervention

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.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes

External Links

•   St. Jude Children's Research Hospital