NCT00002548

SWOG-9321 Melphalan, TBI, and Transplant vs Combo Chemo in Untreated Myeloma

Standard Dose Versus Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma, A Phase III Intergroup Study

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 899 (actual)
• Sponsor: SWOG Cancer Research Network · Network
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed description

OBJECTIVES: * Compare tumor cytoreduction achieved with VBMCP (vincristine/carmustine/melphalan/cyclophosphamide/prednisone) 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 (vincristine/doxorubicin/dexamethasone) 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-PAM/TBI in patients up to age 55 with an HLA-compatible, MLC-nonreactive donor. (As of 8/1/97, 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 and/or 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 (I/II vs IIIA vs IIIB), beta-2 microglobulin at diagnosis (less than 6 micrograms/mL vs at least 6 micrograms/mL), 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 8/1/97) 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 micrograms/mL vs no greater than 3 micrograms/mL 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 stimulation/harvest. Allogeneic BMT arm is permanently closed as of 8/1/97. * 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 patients/year 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 8/1/97, allogeneic arm of study is closed). Approximately 300 patients are expected to be randomized to maintenance vs no further therapy.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
BIOLOGICAL	recombinant interferon alfa	3 million units/m2 SQ Monday-Wednesday -Friday (3 times a week)
DRUG	carmustine	20 mg/m2 I.V. day 1 q 35 days
DRUG	cyclophosphamide	1.5 g/m2 in 100 ml of D5W, IV intravenously over 1 hour every 3 hour x 3 (total dose 4.5 g/m2)
DRUG	dexamethasone	40 mg/day PO or IVPB days 1-4, 9-12, 17-20 q 5 weeks
DRUG	doxorubicin hydrochloride	10 mg/m2/day continuous 1 - 4 q 5 weeks
DRUG	melphalan	140 mg/m2 is given IV within 30 minutes of constitution on Day -5
DRUG	prednisone	40 mg/m2 PO days 1-7 q 35 days
DRUG	vincristine sulfate	0.5 mg/day continuous 1 - 4 q 5 weeks
PROCEDURE	allogeneic bone marrow transplantation	day 0
PROCEDURE	autologous bone marrow transplantation	day 0
PROCEDURE	peripheral blood stem cell transplantation	day 0
RADIATION	radiation therapy	administered in fractionated doses of 150 cGy, 6 - 10 hours apart bid, on Days -4, -3, -2, and -1 (Total 1,200 cGy)

Timeline

• Start date: 1994-01-01
• Primary completion: 2003-10-01
• Completion: 2006-11-01
• First posted: 2003-08-11
• Last updated: 2015-03-06

Locations

34 sites across 1 country: United States