Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002548
Status:
COMPLETED
Last Update Posted:
2015-03-06
First Post:
1999-11-01
Brief Title:
SWOG-9321 Melphalan TBI and Transplant vs Combo Chemo in Untreated Myeloma
Sponsor:
SWOG Cancer Research Network
Organization:
SWOG Cancer Research Network
Study Overview
Official Title:
Standard Dose Versus Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma A Phase III Intergroup Study
Status:
COMPLETED
Status Verified Date:
2015-03
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 Radiation therapy uses high-energy x-rays to damage cancer cells Combining chemotherapy and radiation therapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and radiation therapy and kill more cancer cells It is not yet known which treatment regimen is more effective for multiple myeloma
PURPOSE Randomized phase III trial to compare the effectiveness of melphalan total-body irradiation and peripheral stem cell transplantation with that of combination chemotherapy in treating patients who have previously untreated multiple myeloma
PURPOSE Randomized phase III trial to compare the effectiveness of melphalan total-body irradiation and peripheral stem cell transplantation with that of combination chemotherapy in treating patients who have previously untreated multiple myeloma
Detailed Description:
OBJECTIVES
Compare tumor cytoreduction achieved with VBMCP vincristinecarmustinemelphalancyclophosphamideprednisone vs myeloablative melphalan L-PAM and total-body irradiation TBI with peripheral blood stem cell PBSC rescue in symptomatic myeloma patients with stable or responding disease after induction therapy with VAD vincristinedoxorubicindexamethasone followed by high dose cyclophosphamide plus filgrastim G-CSF
Compare the efficacy of interferon alfa vs no maintenance therapy in those patients achieving at least 75 cytoreduction to either VBMCP or myeloablative therapy with PBSC rescue
Assess allogeneic bone marrow transplantation following the same myeloablative regimen of L-PAMTBI in patients up to age 55 with an HLA-compatible MLC-nonreactive donor As of 8197 permanent partial closure
Determine whether myeloablative therapy with PBSC rescue can extend the duration of survival by 33 compared to results from standard dose VBMCP
Evaluate the toxic effects and possible long term side effects including development of myelodysplastic disease andor acute myeloblastic leukemia associated with these treatments
OUTLINE This is a randomized study Patients are registered at 5 different points with stratification occurring at some of these registrations
Registration I Induction I
Registration II Induction II Patients are stratified according to stage of disease III vs IIIA vs IIIB beta-2 microglobulin at diagnosis less than 6 microgramsmL vs at least 6 microgramsmL and response to Induction I 75-100 regression vs 50-74 regression vs less than 50 regression vs not applicable
Registration III Patients are randomized to allogeneic bone marrow transplant BMT this arm closed as of 8197 or autologous BMT Patients are stratified according to treatment received high dose cyclophosphamide CTX and peripheral blood stem cells PBSC prior to autologous BMT vs prior to chemotherapy and beta-2 microglobulin at this registration less than 2 microgramsmL vs no greater than 3 microgramsmL vs unknown
Registration IV Patients are randomized to maintenance therapy or no further therapy Those patients who are randomized to maintenance therapy are stratified according to treatment autologous BMT vs chemotherapy vs chemotherapy followed by autologous BMT and response to treatment 75-99 regression vs complete response
Registration V Patients receive autologous BMT as in registration III Patients are stratified according to prior best response 50 or better vs less than 50 vs not applicable duration of chemotherapy at least 6 months vs less than 6 months and progression after therapy chemotherapy vs interferon alfa vs observation
Induction I Patients receive vincristine IV and doxorubicin IV by continuous infusion on days 1-4 and dexamethasone IV or orally on days 1-4 9-12 and 17-20 Treatment repeats every 5 weeks for up to 4 courses Patients with progressive disease after 2 courses proceed to PBSC stimulationharvest
Allogeneic BMT arm is permanently closed as of 8197
Autologous BMT Therapy begins 4-8 weeks following high dose cyclophosphamide Patients receive melphalan IV over 1 hour on day -5 and total body irradiation twice a day on days -4 to -1 PBSC are reinfused on day 0 G-CSF SQ is administered beginning on day 1 until blood counts recover
Chemotherapy Patients receive vincristine IV carmustine IV and cyclophosphamide IV on day 1 oral melphalan on days 1-4 and oral prednisone on days 1-7 Treatment repeats every 5 weeks for at least 12 months
Patients who have at least a 75 response to autologous BMT or chemotherapy are randomized to maintenance vs no further therapy Patients who progress on chemotherapy proceed to autologous BMT registration V
Maintenance therapy Therapy begins between 5 and 12 weeks after PBSC rescue Patients receive interferon alfa SQ three times a week Treatment continues for 4 years in the absence of disease progression or unacceptable toxicity
Patients who progress on chemotherapy undergo an autologous BMT within 8 weeks after the last course of chemotherapy
Patients who are randomized to receive no further therapy are observed for 1 year
PROJECTED ACCRUAL A total of 500 patients will be randomized over about 4 years to autologous transplantation vs chemotherapy as follows about 250 patientsyear will be accrued for induction of whom 200 will achieve at least stable disease 125 will be randomized and 15 will have a suitable donor for allogeneic transplant as of 8197 allogeneic arm of study is closed Approximately 300 patients are expected to be randomized to maintenance vs no further therapy
Compare tumor cytoreduction achieved with VBMCP vincristinecarmustinemelphalancyclophosphamideprednisone vs myeloablative melphalan L-PAM and total-body irradiation TBI with peripheral blood stem cell PBSC rescue in symptomatic myeloma patients with stable or responding disease after induction therapy with VAD vincristinedoxorubicindexamethasone followed by high dose cyclophosphamide plus filgrastim G-CSF
Compare the efficacy of interferon alfa vs no maintenance therapy in those patients achieving at least 75 cytoreduction to either VBMCP or myeloablative therapy with PBSC rescue
Assess allogeneic bone marrow transplantation following the same myeloablative regimen of L-PAMTBI in patients up to age 55 with an HLA-compatible MLC-nonreactive donor As of 8197 permanent partial closure
Determine whether myeloablative therapy with PBSC rescue can extend the duration of survival by 33 compared to results from standard dose VBMCP
Evaluate the toxic effects and possible long term side effects including development of myelodysplastic disease andor acute myeloblastic leukemia associated with these treatments
OUTLINE This is a randomized study Patients are registered at 5 different points with stratification occurring at some of these registrations
Registration I Induction I
Registration II Induction II Patients are stratified according to stage of disease III vs IIIA vs IIIB beta-2 microglobulin at diagnosis less than 6 microgramsmL vs at least 6 microgramsmL and response to Induction I 75-100 regression vs 50-74 regression vs less than 50 regression vs not applicable
Registration III Patients are randomized to allogeneic bone marrow transplant BMT this arm closed as of 8197 or autologous BMT Patients are stratified according to treatment received high dose cyclophosphamide CTX and peripheral blood stem cells PBSC prior to autologous BMT vs prior to chemotherapy and beta-2 microglobulin at this registration less than 2 microgramsmL vs no greater than 3 microgramsmL vs unknown
Registration IV Patients are randomized to maintenance therapy or no further therapy Those patients who are randomized to maintenance therapy are stratified according to treatment autologous BMT vs chemotherapy vs chemotherapy followed by autologous BMT and response to treatment 75-99 regression vs complete response
Registration V Patients receive autologous BMT as in registration III Patients are stratified according to prior best response 50 or better vs less than 50 vs not applicable duration of chemotherapy at least 6 months vs less than 6 months and progression after therapy chemotherapy vs interferon alfa vs observation
Induction I Patients receive vincristine IV and doxorubicin IV by continuous infusion on days 1-4 and dexamethasone IV or orally on days 1-4 9-12 and 17-20 Treatment repeats every 5 weeks for up to 4 courses Patients with progressive disease after 2 courses proceed to PBSC stimulationharvest
Allogeneic BMT arm is permanently closed as of 8197
Autologous BMT Therapy begins 4-8 weeks following high dose cyclophosphamide Patients receive melphalan IV over 1 hour on day -5 and total body irradiation twice a day on days -4 to -1 PBSC are reinfused on day 0 G-CSF SQ is administered beginning on day 1 until blood counts recover
Chemotherapy Patients receive vincristine IV carmustine IV and cyclophosphamide IV on day 1 oral melphalan on days 1-4 and oral prednisone on days 1-7 Treatment repeats every 5 weeks for at least 12 months
Patients who have at least a 75 response to autologous BMT or chemotherapy are randomized to maintenance vs no further therapy Patients who progress on chemotherapy proceed to autologous BMT registration V
Maintenance therapy Therapy begins between 5 and 12 weeks after PBSC rescue Patients receive interferon alfa SQ three times a week Treatment continues for 4 years in the absence of disease progression or unacceptable toxicity
Patients who progress on chemotherapy undergo an autologous BMT within 8 weeks after the last course of chemotherapy
Patients who are randomized to receive no further therapy are observed for 1 year
PROJECTED ACCRUAL A total of 500 patients will be randomized over about 4 years to autologous transplantation vs chemotherapy as follows about 250 patientsyear will be accrued for induction of whom 200 will achieve at least stable disease 125 will be randomized and 15 will have a suitable donor for allogeneic transplant as of 8197 allogeneic arm of study is closed Approximately 300 patients are expected to be randomized to maintenance vs no further therapy
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 |
|---|---|---|---|
| U10CA032102 | NIH | CTEP | httpsreporternihgovquickSearchU10CA032102 |
| SWOG-9321 | OTHER | None | None |
| CLB-9312 | OTHER | None | None |
| E-S9321 | OTHER | None | None |
| INT-0141 | OTHER | None | None |