Combination Chemotherapy in Treating Patients With Multiple Myeloma

NCIC Clinical Trials Group

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Drug: dexamethasone; Drug: prednisone; Drug: melphalan

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00002678

CDR0000064328 (Other Identifier)

CAN-NCIC-MY7 (Other Identifier)

NCI-V95-0713 (Other Identifier)

MY7

Details and patient eligibility

About

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.

Full 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.

Enrollment: 595 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

595 participants in 2 patient groups

Melphan plus prednisone

Active Comparator group

Description:

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

Treatment:

Drug: melphalan

Drug: prednisone

Melphan, prednisone pluse dexamethasone

Active Comparator group

Description:

melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; dexamethasone qd x 4 q 28 days after non-progression

Treatment:

Drug: dexamethasone