Combination Chemotherapy in Treating Patients With Multiple Myeloma
This study has been completed.
Sponsor:
NCIC Clinical Trials Group
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00002678
First received: November 1, 1999
Last updated: September 20, 2012
Last verified: September 2011
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective in treating patients with multiple myeloma.
PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients with multiple myeloma.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma and Plasma Cell Neoplasm |
Drug: dexamethasone Drug: melphalan Drug: prednisone |
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: | A COMPARATIVE STUDY OF DEXAMETHASONE VERSUS PREDNISONE (BOTH IN COMBINATION WITH MELPHALAN) AS INDUCTION THERAPY IN UNTREATED SYMPTOMATIC MYELOMA WITH AN ADDITIONAL ASSESSMENT OF DEXAMETHASONE VERSUS NO ADDITIONAL TREATMENT AS MAINTENANCE THERAPY IN NON-PROGRESSING PATIENTS |
Resource links provided by NLM:
Drug Information available for:
Dexamethasone
Prednisone
Melphalan
Dexamethasone acetate
Dexamethasone sodium phosphate
Melphalan hydrochloride
U.S. FDA Resources
Further study details as provided by NCIC Clinical Trials Group:
Primary Outcome Measures:
- Overall survival [ Time Frame: 9 years ] [ Designated as safety issue: No ]
To compare overall survival between:
i) patients receiving melphalan-prednisone and those receiving melphalan-dexamethasone as induction therapy ii) patients maintained by dexamethasone and those on no additional treatment in the subgroup whose disease has not progressed at the time of the 12th induction cycle
Secondary Outcome Measures:
- Time to progression [ Time Frame: 9 years ] [ Designated as safety issue: No ]
- Response rates [ Time Frame: 9 years ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
- Quality of Life [ Time Frame: 9 years ] [ Designated as safety issue: No ]
| Enrollment: | 595 |
| Study Start Date: | May 1995 |
| Study Completion Date: | December 2009 |
| Primary Completion Date: | December 2003 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Melphan plus prednisone
melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; No treatment after stable response.
|
Drug: melphalan
9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeks
Drug: prednisone
100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan
|
|
Active Comparator: Melphan, prednisone pluse dexamethasone
melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; dexamethasone qd x 4 q 28 days after non-progression
|
Drug: dexamethasone
40 mg daily for four days given orally and repeated every 28 days should commence on day 29 of the twelfth cycle of induction therapy.
|
Detailed Description:
OBJECTIVES:
- Compare the overall survival of patients with previously untreated stage I-III multiple myelome treated with melphalan combined with dexamethasone or prednisone as induction therapy.
- Compare the overall survival of patients with stable or responding disease after induction treated with dexamethasone vs observation alone as maintenance therapy.
- Compare the time to progression, response rate, and quality of life of patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, stage (I or II vs III), creatinine (less than 2.0 mg/dL vs 2.0 mg/dL or greater), and intention to use prophylactic bisphosphonate (yes vs no).
Induction: Patients are randomized to 1 of 4 treatment arms.
- Arms I and II: Patients receive induction comprising oral prednisone followed by oral melphalan on days 1-4.
- Arms III and IV: Patients receive induction comprising oral melphalan and oral dexamethasone (DM) on days 1-4 of all courses and DM on days 15-18 of courses 1-3.
Induction for arms I-IV continues every 4 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after induction proceed to maintenance therapy.
Maintenance:
- Arms I and III: Patients undergo observation.
- Arms II and IV: Patients receive oral DM on days 1-4. Maintenance therapy continues every 4 weeks for arms II and IV and every 3 months for arms I and III in the absence of disease progression or unacceptable toxicity. Patients on arms I-IV who develop disease progression proceed to reinduction.
- Reinduction: Patients restart induction on the arm to which they were originally randomized. Reinduction continues every 4 weeks in the absence of stable response lasting 16 weeks, disease progression, or unacceptable toxicity. Patients who achieve a stable response lasting 16 weeks restart maintenance therapy. Patients who experience further disease progression during reinduction are taken off study.
Quality of life is assessed at baseline, on day 1 of courses 1-3 and then every 3 courses during induction, and then every 3 months during maintenance therapy.
Patients are followed every 6 months.
PROJECTED ACCRUAL: A maximum of 600 patients will be accrued for this study within 6 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically proven previously untreated stage I-III multiple myeloma
- Patients with stage I disease must be symptomatic
Must meet at least 1 of the following conditions:
- Plasma cells in osteolytic lesion or soft tissue tumor biopsy
- At least 10% plasmacytosis in bone marrow aspirate and/or biopsy
- Less than 10% plasma cells in bone marrow but at least 1 bony lesion
Detectable serum M-component of IgG, IgA, IgD, or IgE
- If only light chain disease (urine M-protein) present, urinary excretion of light chain (Bence Jones) protein must be at least 1.0 g/24 hours
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-4
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Not specified
Renal:
- Not specified
Other:
- No other concurrent serious illness
- Concurrent diabetes allowed, at the discretion of the treating physician, if changes in insulin requirements can be managed
- No other prior or concurrent malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent immunizations
- No concurrent filgrastim (G-CSF) or other growth factors as prophylaxis
- Concurrent epoetin alfa for anemia allowed
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Prior dexamethasone or prednisone with radiotherapy for spinal cord compression allowed if cumulative dexamethasone dose no greater than 120 mg and cumulative prednisone dose no greater than 792 mg
- Prior or concurrent corticosteroids for hypercalcemia allowed
Radiotherapy:
- See Endocrine therapy
- Prior focal radiotherapy allowed
- Concurrent focal radiotherapy during induction allowed
- Concurrent radiotherapy for palliation (e.g., painful osteolytic lesions or spinal cord compression) allowed
Surgery:
- At least 2 years since prior surgery for radiologic or endoscopic diagnosis of gastric or duodenal ulcer
Other:
- At least 2 years since prior medication for radiologic or endoscopic diagnosis of gastric or duodenal ulcer
- Prior or concurrent bisphosphonates for hypercalcemia allowed
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002678
Show 37 Study Locations
Show 37 Study LocationsSponsors and Collaborators
NCIC Clinical Trials Group
Investigators
| Study Chair: | Chaim Shustik, MD | Royal Victoria Hospital - Montreal |
More Information
Additional Information:
Publications:
Shustik C, Belch A, Robinson S, et al.: Dexamethasone (dex) maintenance versus observation (obs) in patients with previously untreated multiple myeloma: a National Cancer Institute of Canada Clinical Trials Group study: MY.7. [Abstract] J Clin Oncol 22 (Suppl 14): A-6510, 560s, 2004.
Shustik C, Belch A, Meyer R, et al.: Melphalan-dexamethasone is not superior to melphalan-prednisone as induction therapy in multiple myeloma. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1191, 2001.
| Responsible Party: | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00002678 History of Changes |
| Other Study ID Numbers: | MY7, CAN-NCIC-MY7, NCI-V95-0713, CDR0000064328 |
| Study First Received: | November 1, 1999 |
| Last Updated: | September 20, 2012 |
| Health Authority: | Canada: Health Canada |
Keywords provided by NCIC Clinical Trials Group:
|
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma |
Additional relevant MeSH terms:
|
Neoplasms Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Neoplasms by Histologic Type Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |
Dexamethasone acetate Dexamethasone Prednisone Dexamethasone 21-phosphate Melphalan BB 1101 Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Gastrointestinal Agents |
ClinicalTrials.gov processed this record on May 19, 2013