Combination Chemotherapy in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	NCIC Clinical Trials Group
Information provided by (Responsible Party):	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00002678

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 III

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:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Prednisone Dexamethasone acetate Doxiproct plus Melphalan Sarcolysin 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 2009 (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

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

Study Chair:

Chaim Shustik, MD

Royal Victoria Hospital - Montreal

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Shustik C, Belch A, Robinson S, Rubin SH, Dolan SP, Kovacs MJ, Grewal KS, Walde D, Barr R, Wilson J, Gill K, Vickars L, Rudinskas L, Sicheri DA, Wilson K, Djurfeldt M, Shepherd LE, Ding K, Meyer RM. A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7. Br J Haematol. 2007 Jan;136(2):203-11.

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 27, 2011
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 February 09, 2012