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

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00002548
First received: November 1, 1999
Last updated: May 21, 2013
Last verified: May 2013
  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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002548

  Show 34 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Investigators
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:
Van Ness BG, Crowley JC, Ramos C, et al.: SNP genotypes show association with common toxicities during both VAD induction and high dose melphalan with autologous transplant support in intergroup trial S9321 for myeloma: from the Bank on a Cure. [Abstract] Blood 106 (11): A-3488, 2005.
Crowley J, Fonseca R, Greipp P, et al.: Comparable survival in newly diagnosed multiple myeloma (MM) after VAD induction with high dose therapy using melphalan 140mg/m2 + TBI 12 Gy (MEL+TBI) versus standard therapy with VBMCP and no benefit from interferon (IFN) maintenance: final clinical results of intergroup trial S9321 in the context of IFM 90 and MRC VII trials. [Abstract] Blood 104 (11): A-539, 2004.
Santana-Davila R, Crowley J, Durie B, et al.: Genetic polymorphisms associated with clinical outcome in the intergroup trial S9321, comparing high dose therapy with standard dose therapy for myelomaon, on behalf of ECOG, SWOG, CALGB, and the Bank on a Cure. [Abstract] Blood 104 (11): A-1495, 2004.
Lee CK, McCoy J, Anderson KC, et al.: Long-term follow-up of previously untreated symptomatic myeloma patients treated with myeloablative therapy and sibling-matched allogeneic transplantation of the SWOG study 9321. [Abstract] Blood 100 (11 pt 1): A-1644, 2002.
Greipp PR, Jacobson JL, Crowley JJ, et al.: BETA 2 microglobulin (beta 2M) and plasma cell labeling index (PCLI) constitute a strong prognostic index in the SWOG intergroup transplant trial S9321: observations on gender and age. [Abstract] Blood 96 (11 pt 1): A-653, 152a, 2000.
Desika R, Salmon S, Anderson K, et al.: Planned melphalan-total body irradiation (MEL-TBI) - based allogeneic transplantation for multiple myeloma (MM) up to age 55: an intergroup experience (CALGB, ECOG and SWOG) under the auspices of the Southwest Oncology Group (SWOG 9321). [Abstract] Blood 94 (10 Pt 1): A-1546, 346a, 1999.
van Ness BG, Ramos C, Kumar V, et al.: Analytical approaches for the BOAC SNP panel association with progression free survival in myeloma. [Abstract] Blood 112 (11): A-2715, 2008.
Crowley JJ, McCoy J, LeBlanc M, et al.: Extreme regression: a statistical technique for finding good or poor prognostic groups, illustrated using myeloma patient data from Intergroup trial S9321. [Abstract] Blood 104 (11): A-5202, 2004.
Greipp PR, Kumar S, Blood EA, et al.: A simple classification to identify poor-risk untreated myeloma. [Abstract] Blood 100 (11 Pt 1): A-2351, 598a, 2002.
Tian E, Bumm K, Xiao Y, et al.: A protocol for triple color interphase FISH on archived bone marrow biopsies from myeloma prepared with precipitating fixatives. [Abstract] Blood 96 (11 pt 1): A-665, 155a, 2000.
Rajkumar V, Leong T, Fonseca R, et al.: Bone marrow angiogenesis has prognostic value in multiple myeloma: an Eastern Cooperative Oncology Group study. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A68, 19a, 1999.

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
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Cyclophosphamide
Dexamethasone
Doxorubicin
Interferon-alpha
Interferons
Liposomal doxorubicin
Melphalan
Prednisone
Vincristine
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimitotic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 24, 2014