SWOG-9321 Melphalan, TBI, and Transplant vs Combo Chemo in Untreated Myeloma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma |
Biological: recombinant interferon alfa Drug: carmustine Drug: cyclophosphamide Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: melphalan Drug: prednisone Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Standard Dose Versus Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma, A Phase III Intergroup Study |
- survival [ Time Frame: 3 years from randomization ] [ Designated as safety issue: No ]
| Enrollment: | 899 |
| Study Start Date: | January 1994 |
| Study Completion Date: | November 2006 |
| Primary Completion Date: | October 2003 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: HDCTX and PBSC
High dose chemotherapy with peripheral blood stem cells High dose chemotherapy with peripheral blood stem cells IND (q 5 weeks): vincristine 0.5 mg/d cont IV D1-4; adriamycin 10mg/m2/d cont IV D1-4; dex 40 mg/d PO or IVPB D1-4, 9-12, 17-20 2nd Reg: cyclophosphamide 1.5g/m2 IV over 1 hr every 3 hrs x 3 (4.5g/m2 total); MESNA 4.5 g/m2 24 hr IV start with cyclo; GCSF 0.25 mg/m2/d SQ; PBSC collection Chemo: vincristine 1.2 mg/m2 IV D1, BCNU 20 mg/m2 IV D1, melphalan 8 mg/m2 PO D1-4, cyclophosphamide 400 mg/m2 IV D1, prednisone 40 mg/m2 PO D1-7 |
Drug: doxorubicin hydrochloride
10 mg/m2/day continuous 1 - 4 q 5 weeks
Other Name: Adriamycin
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: peripheral blood stem cell transplantation
day 0
|
|
Experimental: HDCTX with PBSC and Autologous BMT
High dose chemotherapy with peripheral blood stem cells and autologous bone marrow transplant High dose chemotherapy with peripheral blood stem cells and autologous bone marrow transplant High dose chemotherapy with peripheral blood stem cells IND (q 5 weeks): vincristine 0.5 mg/d cont IV D1-4; adriamycin 10mg/m2/d cont IV D1-4; dex 40 mg/d PO or IVPB D1-4, 9-12, 17-20 2nd Reg: cyclophosphamide 1.5g/m2 IV over 1 hr every 3 hrs x 3 (4.5g/m2 total); MESNA 4.5 g/m2 24 hr IV start with cyclo; GCSF 0.25 mg/m2/d SQ; PBSC collection Auto Trans: Mel 140mg/m2 IV D-5; TBI 150cGy D-4, -3, -2, -1; infusion D0 |
Drug: carmustine
20 mg/m2 I.V. day 1 q 35 days
Other Name: BCNU
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)
Other Name: cytoxan
Drug: dexamethasone
40 mg/day PO or IVPB days 1-4, 9-12, 17-20 q 5 weeks
Other Name: steroid, decadron
Drug: doxorubicin hydrochloride
10 mg/m2/day continuous 1 - 4 q 5 weeks
Other Name: Adriamycin
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
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)
|
|
Experimental: HDCTX with PBSC and interferon
High dose chemotherapy with peripheral blood stem cells and interferon Experimental: HDCTX with PBSC and interferon High dose chemotherapy with peripheral blood stem cells and interferon High dose chemotherapy with peripheral blood stem cells IND (q 5 weeks): vincristine 0.5 mg/d cont IV D1-4; adriamycin 10mg/m2/d cont IV D1-4; dex 40 mg/d PO or IVPB D1-4, 9-12, 17-20 2nd Reg: cyclophosphamide 1.5g/m2 IV over 1 hr every 3 hrs x 3 (4.5g/m2 total); MESNA 4.5 g/m2 24 hr IV start with cyclo; GCSF 0.25 mg/m2/d SQ; PBSC collection Chemo: vincristine 1.2 mg/m2 IV D1, BCNU 20 mg/m2 IV D1, melphalan 8 mg/m2 PO D1-4, cyclophosphamide 400 mg/m2 IV D1, prednisone 40 mg/m2 PO D1-7 IFN: IFN 3 million units/m2 MWF SQ |
Biological: recombinant interferon alfa
3 million units/m2 SQ Monday-Wednesday -Friday (3 times a week) Other Name: IFN, alpha interferon
Drug: doxorubicin hydrochloride
10 mg/m2/day continuous 1 - 4 q 5 weeks
Other Name: Adriamycin
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: peripheral blood stem cell transplantation
day 0
|
|
Experimental: HDCTX with PBSC and transplant plus IFN
High dose chemotherapy with peripheral blood stem cells and autologous bone marrow transplant plus alpha interferon Experimental: HDCTX with PBSC and transplant plus IFN High dose chemotherapy with peripheral blood stem cells and autologous bone marrow transplant plus alpha interferon High dose chemotherapy with peripheral blood stem cells IND (q 5 weeks): vincristine 0.5 mg/d cont IV D1-4; adriamycin 10mg/m2/d cont IV D1-4; dex 40 mg/d PO or IVPB D1-4, 9-12, 17-20 2nd Reg: cyclophosphamide 1.5g/m2 IV over 1 hr every 3 hrs x 3 (4.5g/m2 total); MESNA 4.5 g/m2 24 hr IV start with cyclo; GCSF 0.25 mg/m2/d SQ; PBSC collection Trans: Mel 140mg/m2 IV D-5; TBI 150cGy D-4, -3, -2, -1; infusion D0 IFN: 3 million units/m2 MWF SQ |
Biological: recombinant interferon alfa
3 million units/m2 SQ Monday-Wednesday -Friday (3 times a week) Other Name: IFN, alpha interferon
Drug: carmustine
20 mg/m2 I.V. day 1 q 35 days
Other Name: BCNU
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)
Other Name: cytoxan
Drug: dexamethasone
40 mg/day PO or IVPB days 1-4, 9-12, 17-20 q 5 weeks
Other Name: steroid, decadron
Drug: doxorubicin hydrochloride
10 mg/m2/day continuous 1 - 4 q 5 weeks
Other Name: Adriamycin
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
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)
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Newly diagnosed, active multiple myeloma of any stage requiring treatment
- Smoldering myeloma (Durie-Salmon stage I) must have a 25% or greater increase in M component levels and/or Bence-Jones protein excretion or development of symptoms
Quantifiable M component of IgG, IgA, IgD, IgE, and/or urinary kappa or lambda light chain (Bence-Jones protein) excretion required
- Plasmacytosis of at least 30% allowed for non-secretory disease or secretory disease without quantifiable protein
- IgM peaks excluded
Evaluation of siblings as potential allogeneic bone marrow transplant donors required for patients 55 years of age and younger (As of 8/1/97, permanently closed)
- HLA followed by DR and MLC testing required
Renal failure, even on dialysis, eligible provided:
- Cause is attributed to myeloma (Bence-Jones protein or hypercalcemia)
- Duration does not exceed 2 months
If medically appropriate, the following conditions should be treated prior to registration:
- Pathologic fractures
- Pneumonia at diagnosis
- Hyperviscosity with shortness of breath
PATIENT CHARACTERISTICS:
Age:
- 70 and under
Performance status:
- SWOG 0-2 (SWOG 3 or 4 based solely on bone pain allowed)
Hematopoietic:
- Not specified
Hepatic:
- Not specified
Renal:
- See Disease Characteristics
Cardiovascular:
- Normal ejection fraction by ECHO or MUGA
- No myocardial infarction within 6 months
- No unstable angina
- No difficult to control congestive heart failure
- No uncontrolled hypertension
- No difficult to control arrhythmias
- No history of chronic cerebral vascular accident
Pulmonary:
- No history of chronic obstructive or restrictive pulmonary disease
- Pulmonary function studies and DLCO at least 50% of predicted except for demonstrated myeloma involvement on bronchoscopy and/or open lung biopsy
Other:
- No uncontrolled diabetes
- No significant comorbid medical condition
- No uncontrolled, life-threatening infection
- No prior malignancy within 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
- No prior malignancy treated with cytotoxic drugs used on this protocol
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
No prior radiotherapy except local radiotherapy provided the following cumulative dose limits for prior dose plus potential TBI dose on protocol are not exceeded:
- Less than 5,000 cGy to bone
- Less than 4,000 cGy to mediastinum, heart, small bowel, brain, and spinal cord
- Less than 2,000 cGy to the liver
- Less than 1,500 cGy to the kidney and lungs
Surgery:
- Not specified
Contacts and Locations
Show 34 Study Locations| Study Chair: | Bart Barlogie, MD | University of Arkansas |
| Study Chair: | Kenneth C. Anderson, MD | Dana-Farber Cancer Institute |
| Study Chair: | Robert A. Kyle, MD | Mayo Clinic |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00002548 History of Changes |
| Other Study ID Numbers: | CDR0000063310, SWOG-9321, CLB-9312, E-S9321, INT-0141, U10CA032102 |
| Study First Received: | November 1, 1999 |
| Last Updated: | May 21, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Southwest Oncology Group:
|
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Interferon-alpha |
Interferon Alfa-2a Interferons Cyclophosphamide Melphalan Carmustine Dexamethasone Doxorubicin Prednisone Vincristine Dexamethasone acetate Dexamethasone 21-phosphate BB 1101 Antiviral Agents Anti-Infective Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013