Combination Chemotherapy in Treating Patients With Multiple Myeloma

NCT ID: NCT00002678

Last Updated: 2020-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

595 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-06-02

Study Completion Date

2009-12-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Multiple Myeloma and Plasma Cell Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Melphan plus prednisone

melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; No treatment after stable response.

Group Type ACTIVE_COMPARATOR

melphalan

Intervention Type DRUG

9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeks

prednisone

Intervention Type DRUG

100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan

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

Group Type ACTIVE_COMPARATOR

dexamethasone

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

melphalan

9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeks

Intervention Type DRUG

prednisone

100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NCIC Clinical Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chaim Shustik, MD

Role: STUDY_CHAIR

Royal Victoria Hospital - Montreal

Locations

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St. Mary's/Duluth Clinic Health System

Duluth, Minnesota, United States

Site Status

Tom Baker Cancer Center - Calgary

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

Providence Health Care - Vancouver

Vancouver, British Columbia, Canada

Site Status

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

Site Status

Moncton Hospital

Moncton, New Brunswick, Canada

Site Status

Doctor Leon Richard Oncology Centre

Moncton, New Brunswick, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Newfoundland Cancer Treatment and Research Foundation

St. John's, Newfoundland and Labrador, Canada

Site Status

Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada

Site Status

William Osler Health Centre

Brampton, Ontario, Canada

Site Status

Northeastern Ontario Regional Cancer Centre, Sudbury

Greater Sudbury, Ontario, Canada

Site Status

Cancer Care Ontario-Hamilton Regional Cancer Centre

Hamilton, Ontario, Canada

Site Status

Kingston Regional Cancer Centre

Kingston, Ontario, Canada

Site Status

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, Canada

Site Status

Trillium Health Centre

Mississauga, Ontario, Canada

Site Status

Credit Valley Hospital

Mississauga, Ontario, Canada

Site Status

Southlake Regional Health Centre

Newmarket, Ontario, Canada

Site Status

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Site Status

Algoma District Medical Group

Sault Ste. Marie, Ontario, Canada

Site Status

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, Canada

Site Status

Toronto East General Hospital

Toronto, Ontario, Canada

Site Status

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

Site Status

St. Michael's Hospital - Toronto

Toronto, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Humber River Regional Hospital

Weston, Ontario, Canada

Site Status

Cancer Care Ontario - Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Site Status

Queen Elizabeth Hospital, PEI

Charlottetown, Prince Edward Island, Canada

Site Status

CHUS-Hopital Fleurimont

Fleurimont, Quebec, Canada

Site Status

Hopital Charles Lemoyne

Greenfield Park, Quebec, Canada

Site Status

McGill University

Montreal, Quebec, Canada

Site Status

Hopital de L'Enfant Jesus

Québec, Quebec, Canada

Site Status

Hopital du Saint-Sacrement, Quebec

Québec, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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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. doi: 10.1111/j.1365-2141.2006.06405.x.

Reference Type RESULT
PMID: 17233817 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT

Other Identifiers

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CAN-NCIC-MY7

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-V95-0713

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064328

Identifier Type: OTHER

Identifier Source: secondary_id

MY7

Identifier Type: -

Identifier Source: org_study_id

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