Autologous Stem Cell Transplant Followed By Donor Stem Cell Transplant In Treating Patients With Relapsed or Refractory Lymphoma
This phase I/II trial is studying how well giving autologous stem cell transplant followed by donor stem cell transplant works in treating patients with relapsed or refractory lymphoma. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Childhood Burkitt Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Splenic Marginal Zone Lymphoma
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: autologous hematopoietic stem cell transplantation
Biological: therapeutic autologous lymphocytes
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial|
- Engraftment of HLA identical PBSC allografts [ Time Frame: Day 56 ] [ Designated as safety issue: Yes ]The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).
- Non-relapse mortality [ Time Frame: Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting ] [ Designated as safety issue: No ]The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).
- Disease-free survival and overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]Though progression-free survival (PFS) and overall survival (OS) will be analyzed for the trial as a whole, chemosensitive and chemoresistant patients will be analyzed separately for PFS and OS for comparison to their respective historical controls. These groups will be looked at separately to gather preliminary data on whether or not there appears to be a difference in the PFS among patients who had chemosensitive vs chemoresistant disease.
|Study Start Date:||September 1999|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tandem transplantation)
See Detailed Description
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic transplantation
Other Names:Drug: cyclophosphamide
Other Names:Radiation: total-body irradiation
Other Name: TBIDrug: carmustine
Other Names:Drug: etoposide
Other Names:Drug: cytarabine
Other Names:Drug: melphalan
Other Names:Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantationDrug: fludarabine phosphate
Other Names:Drug: mycophenolate mofetil
Other Names:Drug: cyclosporine
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous transplantationBiological: therapeutic autologous lymphocytes
IV donor lymphocyte infusion
I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy) +/- fludarabine, 90 mg/m^2 and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.
II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting.
I. To determine the disease free survival and overall survival of non-myeloablative allografting following autologous PBSCT.
CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.
TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients with related donors) or 100 (patients with unrelated donors) followed by taper to day 180. Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day 96 (patients with unrelated donors).
Some patients may undergo donor lymphocyte infusion if there is evidence of disease progression and no evidence of graft-vs-host disease (GVHD).
After completion of study treatment, patients are followed up at 1, 1.5, 2, and 3 years and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005803
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: David G. Maloney 206-667-5616|
|Principal Investigator: David G. Maloney|
|VA Puget Sound Health Care System||Recruiting|
|Seattle, Washington, United States, 98101|
|Contact: Thomas R. Chauncey 206-762-1010|
|Principal Investigator: Thomas R. Chauncey|
|Leipzig, Germany, D-04103|
|Principal Investigator:||David Maloney||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|