Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00070187
Status:
COMPLETED
Last Update Posted:
2013-10-17
First Post:
2003-10-03
Brief Title:
Immunotherapy Using Cyclosporine Interferon Gamma and Interleukin-2 After High-Dose Myeloablative Chemotherapy With Autologous Stem Cell Transplantation in Treating Patients With Refractory or Relapsed Hodgkins Lymphoma
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Phase IIIII Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for RefractoryRelapsed Hodgkin Disease
Status:
COMPLETED
Status Verified Date:
2013-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells Giving immunotherapy using cyclosporine interferon gamma and interleukin-2 after stem cell transplantation may help the transplanted cells make an immune response and kill any remaining cancer cells It is not yet known whether high-dose chemotherapy followed by autologous stem cell transplantation is more effective with or without immunotherapy
PURPOSE This randomized phase IIIII trial is studying how well high-dose chemotherapy followed by autologous stem cell transplantation cyclosporine interferon gamma and interleukin-2 works and compares it to high-dose chemotherapy followed by autologous stem cell transplantation only in treating patients with refractory or relapsed Hodgkins lymphoma
PURPOSE This randomized phase IIIII trial is studying how well high-dose chemotherapy followed by autologous stem cell transplantation cyclosporine interferon gamma and interleukin-2 works and compares it to high-dose chemotherapy followed by autologous stem cell transplantation only in treating patients with refractory or relapsed Hodgkins lymphoma
Detailed Description:
OBJECTIVES
Primary
Phase II
Determine the feasibility and toxicity of immunotherapy comprising cyclosporine interferon gamma and interleukin-2 after high-dose myeloablative chemotherapy with autologous stem cell transplantation ASCT in patients with refractory or relapsed Hodgkins lymphoma
Phase II part of the study was completed and should have proceeded to Phase III however long delay occurred due to some proposed protocol changes to Phase III so long that the study got permanently closed
Phase III
Compare the event-free and overall survival of patients treated with vs without this immunotherapy regimen
Secondary
Determine the event-free and overall survival rates toxic effects and response rates to reinduction chemotherapy followed by hyperfractionated involved-field radiotherapy high-dose chemotherapy comprising carmustine etoposide cytarabine and melphalan and ASCT in these patients
Correlate tumor biologic characteristics with response in patients treated with these regimens
Determine the effectiveness of this immunotherapy regimen in producing autologous graft-vs-host disease GVHD and auto-reactive cytotoxic T-lymphocyte activity in these patients
Correlate greater levels of autologous GVHD and in vitro cytolytic activity with improved event-free and overall survival in patients treated with these regimens
Determine whether treatment with immunotherapy can overcome the negative prognostic significance of p53 mutation and high serum levels of interleukin-10 and interleukin-2 receptor in these patients
Determine the genotoxicity of retrieval therapy and the incidence of hypermutability by longitudinal genotoxic biomonitoring in these patients
Correlate HLA class II invariant peptide CLIP expression in tumor cells with improved event-free and overall survival in patients treated with immunotherapy regimen
OUTLINE This is a nonrandomized multicenter phase II study followed by a randomized multicenter phase III study Patients are stratified according to study phase II vs III
Patients receive 2 courses of salvage induction therapy on COG-AHOD00P1 or equivalent Within 2-5 weeks after completion of salvage induction therapy patients receive protocol therapy
Phase II All patients receive the following treatment
Hyperfractionated involved-field radiotherapy Patients who have completed prior salvage induction therapy and have not received full tissue tolerance from prior radiotherapy may receive hyperfractionated involved-field radiotherapy twice daily for 7 days
High-dose preparative regimen Beginning within 7 days after radiotherapy patients receive carmustine IV over 3 hours on day -6 etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2 and melphalan IV over 30 minutes on day -1
Autologous stem cell transplantation Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0 Patients then receive filgrastim G-CSF subcutaneously SC or IV beginning on day 1 and continuing until blood counts recover
Immunotherapy Patients receive cyclosporine IV twice daily beginning on day 0 and continuing until the completion of the course of interferon gamma and interleukin-2 When sufficiently recovered patients also receive interferon gamma SC every other day for 10 doses Beginning 2 days after the start of interferon gamma patients also receive interleukin-2 SC once daily for 18 days
Phase III Patients who respond to prior salvage induction therapy are randomized to 1 of 2 treatment arms Patients who have progressive disease after 2 courses of prior salvage induction therapy are assigned to arm I
Arm I Patients receive treatment as in phase II
Arm II Patients receive treatment as in phase II without immunotherapy In both phases treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed at 1 year
PROJECTED ACCRUAL A total of 156 patients 25 for phase II and 131 for phase III will be accrued for this study within 54 years
Primary
Phase II
Determine the feasibility and toxicity of immunotherapy comprising cyclosporine interferon gamma and interleukin-2 after high-dose myeloablative chemotherapy with autologous stem cell transplantation ASCT in patients with refractory or relapsed Hodgkins lymphoma
Phase II part of the study was completed and should have proceeded to Phase III however long delay occurred due to some proposed protocol changes to Phase III so long that the study got permanently closed
Phase III
Compare the event-free and overall survival of patients treated with vs without this immunotherapy regimen
Secondary
Determine the event-free and overall survival rates toxic effects and response rates to reinduction chemotherapy followed by hyperfractionated involved-field radiotherapy high-dose chemotherapy comprising carmustine etoposide cytarabine and melphalan and ASCT in these patients
Correlate tumor biologic characteristics with response in patients treated with these regimens
Determine the effectiveness of this immunotherapy regimen in producing autologous graft-vs-host disease GVHD and auto-reactive cytotoxic T-lymphocyte activity in these patients
Correlate greater levels of autologous GVHD and in vitro cytolytic activity with improved event-free and overall survival in patients treated with these regimens
Determine whether treatment with immunotherapy can overcome the negative prognostic significance of p53 mutation and high serum levels of interleukin-10 and interleukin-2 receptor in these patients
Determine the genotoxicity of retrieval therapy and the incidence of hypermutability by longitudinal genotoxic biomonitoring in these patients
Correlate HLA class II invariant peptide CLIP expression in tumor cells with improved event-free and overall survival in patients treated with immunotherapy regimen
OUTLINE This is a nonrandomized multicenter phase II study followed by a randomized multicenter phase III study Patients are stratified according to study phase II vs III
Patients receive 2 courses of salvage induction therapy on COG-AHOD00P1 or equivalent Within 2-5 weeks after completion of salvage induction therapy patients receive protocol therapy
Phase II All patients receive the following treatment
Hyperfractionated involved-field radiotherapy Patients who have completed prior salvage induction therapy and have not received full tissue tolerance from prior radiotherapy may receive hyperfractionated involved-field radiotherapy twice daily for 7 days
High-dose preparative regimen Beginning within 7 days after radiotherapy patients receive carmustine IV over 3 hours on day -6 etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2 and melphalan IV over 30 minutes on day -1
Autologous stem cell transplantation Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0 Patients then receive filgrastim G-CSF subcutaneously SC or IV beginning on day 1 and continuing until blood counts recover
Immunotherapy Patients receive cyclosporine IV twice daily beginning on day 0 and continuing until the completion of the course of interferon gamma and interleukin-2 When sufficiently recovered patients also receive interferon gamma SC every other day for 10 doses Beginning 2 days after the start of interferon gamma patients also receive interleukin-2 SC once daily for 18 days
Phase III Patients who respond to prior salvage induction therapy are randomized to 1 of 2 treatment arms Patients who have progressive disease after 2 courses of prior salvage induction therapy are assigned to arm I
Arm I Patients receive treatment as in phase II
Arm II Patients receive treatment as in phase II without immunotherapy In both phases treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed at 1 year
PROJECTED ACCRUAL A total of 156 patients 25 for phase II and 131 for phase III will be accrued for this study within 54 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| COG-AHOD0121 | OTHER | Childrens Oncology Group | None |
| CDR0000330135 | OTHER | None | None |