Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.
Drug: Antithymocyte globulin
Drug: Mycophenolate mofetil
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma|
- Event-free survival [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]
- Incidence of chemotherapy-associated pneumonitis [ Time Frame: 3 months following the enrollment of the last participant. ] [ Designated as safety issue: Yes ]
- Overall and non-relapse mortality rate [ Time Frame: Two years after the last participant is enrolled ] [ Designated as safety issue: Yes ]
- Kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: Two years after the last participant is enrolled ] [ Designated as safety issue: Yes ]
- Incidence and extent of acute and chronic Graft versus host disease [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2007|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: hematopoietic cell transplantation
autologous hematopoietic cell transplantation (AHCT) followed by total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) followed by matched allogeneic hematopoietic cell transplantation.
Other Names:Drug: Carmustine
15mg/kg, IV over 2 hours
Other Name: BiCNUDrug: Etoposide
60mg/kg, IV over 4 hours
Other Names:Drug: Filgrastim
Other Names:Drug: Antithymocyte globulin
Other Name: ATGDrug: Cyclosporine
5mg/kgbid,variable, po or IV
Other Names:Drug: Mycophenolate mofetil
15mg/kg,variable, po or iv
Other Names:Drug: rituximab
Currently, patients with recurrent or primary refractory non-Hodgkin's lymphoma are treated with second-line chemotherapy (usually 2-3 courses) for the purpose of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells are mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. The standard high dose regimen consists of augmented carmustine, etoposide and cyclophosphamide. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease.
Past studies conducted at Stanford have included a group of 17 patients with transformed lymphoma who received autologous transplants, the median EFS and OS were 1.48 and 2.7 years respectively with a 7-year survival of only 20%. In comparison, patients with chemosensitive follicular lymphoma who received the same regimen also had a poor median EFS of 1.3 years, but the median survival was 6.7 years. The outcomes for patients with chemotherapy-resistant relapsed NHL is also poor with EFS in the range of 20% in many studies of autologous transplantation.
These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that has been taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide and cyclophosphamide with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00481832
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Wen-Kai Weng||Stanford University|