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The Treatment of Multiple Myeloma Utilizing VBMCP Chemotherapy Alternating With High-Dose Cyclophosphamide and Alpha2b-Interferon Versus VBMCP: A Phase III Study for Previously Untreated Multiple Myeloma

Phase 3
18 Years
Not Enrolling
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Thank you

Trial Information

The Treatment of Multiple Myeloma Utilizing VBMCP Chemotherapy Alternating With High-Dose Cyclophosphamide and Alpha2b-Interferon Versus VBMCP: A Phase III Study for Previously Untreated Multiple Myeloma


I. To compare response rate, time to response, duration of response, toxicity, and survival
in the two regimens (vincristine sulfate, carmustine, melphalan, cyclophosphamide,
prednisone [VBMCP] vs. VBMCP alternating with high-dose cyclophosphamide and then with
recombinant interferon alfa-2b [r alpha2b-IFN]) in patients with previously untreated
multiple myeloma.

II. To determine the value of the ancillary laboratory studies to predict response and


INDUCTION PHASE: Patients receive VBMCP comprising vincristine sulfate intravenously (IV) on
day 1, carmustine IV on day 1, melphalan orally (PO) on days 1-4, cyclophosphamide IV on day
1, and prednisone PO on days 1-7. Treatment repeats every 35 days for 2 courses in the
absence of disease progression or unacceptable toxicity.

CONSOLIDATION PHASE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive VBMCP as in the induction phase. Courses repeat every 35 days in the
absence of disease progression or unacceptable toxicity.

ARM B: Patients receive vincristine sulfate, carmustine, and melphalan as in the induction
phase, high-dose cyclophosphamide IV on days 1-4 and prednisone PO on days 1-4 during
courses 3 and 5. Patients receive VBMCP as in the induction phase during even numbered
courses. Patients receive recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3,
5, 8, 10, 12, 15, 17, 19, and 22 during odd courses beginning course 7. Treatment repeats
every 35 days for courses 3-5, every 21 days for even courses beginning course 6, and every
22 days for odd courses beginning course 7 in the absence of disease progression or
unacceptable toxicity.

In both arms, treatment continues for up to 2 years.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Patients must have a diagnosis of multiple myeloma confirmed by the presence of:

- Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or
biopsy-proven plasmacytoma

- In addition, at least 1 of the following ancillary criteria must be documented:

- M-protein in the serum

- M-protein in the urine

- Radiographic evidence of osteolytic lesions (generalized osteoporosis
qualifies only if the bone marrow aspirate contains >= 20% plasma cells)

- Patients must have measurable disease; the following will constitute measurable
disease; tests used to document measurable disease must be done within two weeks
prior to registration; a bone marrow biopsy performed =< 6 weeks prior to
registration is acceptable; Note: If present, all of these parameters must be
followed for response

- Serum M-protein >= 1.0 g/dL by serum protein electrophoresis

- Urine M-protein (light chain) excretion > 200 mg/24 hours by urine protein

- Measurable plasmacytoma(s) of soft tissue (must be biopsy proven)

- Bone marrow plasmacytosis >= 20%

- Patients must not have been previously treated with chemotherapy; prior treatment of
hypercalcemia with corticosteroids, bisphosphonates, or other agents does not
disqualify the patient

- Patients refuses entry or is ineligible for S9321; Note: S9321, "Standard Dose Versus
Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma" has
priority over E5A93; patients with previously untreated multiple myeloma should be
entered on S9321; patients who are ineligible for or decline entry to S9321 should be
entered on E5A93 and E3A93 if eligible

- Patients treated with local radiotherapy to > 15% of the bone marrow area are
ineligible; patients who require concurrent radiotherapy should have entry to the
protocol deferred until the radiotherapy is completed; if, in the physician's
opinion, the delay in systemic therapy would itself pose undue risk, the patient may
be entered and receive concurrent radiotherapy; in this situation, for the first
VBMCP cycle, Melphalan, BCNU and Cyclophosphamide should be given at 75% of the dose

- Patients with Stages I, II, or III disease according to a modification of the
clinical staging system by Durie and Salmon are eligible; staging should be based on
values obtained at the time of diagnosis unless patient has had a more abnormal value
prior to supportive treatment, transfusion, etc.; include only values obtained prior
to initiation of protocol treatment

- Pretreatment x-rays must be done within 6 weeks of registration; copies of the bone
x-ray reports are required and must be submitted with on-study forms

- Bone marrow slides must be submitted

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Platelet count >= 50,000/mm^3

- Creatinine =< 5.0 mg/dL (NOTE: Patients with creatinine 2.0-5.0 mg/dL may be admitted
to this study but must receive altered doses and schedules of therapy)

- Patients requiring dialysis are not eligible

- Bilirubin =< 2.0 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x upper limit of normal

- Alkaline phosphatase =< 2.5 x upper limit of normal

- No myocardial infarction within previous 6 months, no significant arrhythmia within
the prior 3 months; if hypertension is present, it should be under control prior to
study entry

- Patients with a history of congestive heart failure or myocardial infarction must
have a normal myocardial ejection fraction as determined by echogram or multiple gate
acquisition (MUGA) scan

- No patient with angina requiring nitrates or beta blockers, or with a history of
thrombophlebitis or pulmonary emboli within the previous 6 months and currently
requiring anticoagulants

- Patients with concurrent reversible conditions, e.g., infection, hyperuricemia, cord
compression, hyperviscosity syndrome, central nervous system (CNS) complications, or
renal disease may be entered into this study after appropriate therapy for these
complications is initiated and the condition is controlled; therapy must be fully
documented and dated on the on-study form; Note: Hypercalcemia patients may be
entered directly on study and may receive corticosteroids, bisphosphonates, or other
agents as needed for control of hypercalcemia; Note: Anemia patients may be entered
directly on study and may receive erythropoietin (epoetin alfa: Procrit, Epogen,
Aranesp, etc.) or other agents as needed for control of anemia

- No smoldering multiple myeloma, nonsecretory myeloma, localized plasmacytomas,
monoclonal gammopathy of undetermined significance (MGUS), or primary systemic
amyloidosis (AL)

- No patient with second malignancies except: those treated with surgery alone who are
disease free > 5 years or patients whose only other malignancy is non-melanoma skin
cancer or carcinoma in situ of the cervix

- Patients >= 70 years must have a performance status of 0-2, and be specifically
evaluated by their physician to determine if they can tolerate either regimen; they
should not enter the study if the physician feels that they would be unable to
tolerate either regimen

- Female patients of childbearing potential must have a negative pregnancy test
documented before entering this study; these patients must be provided adequate
guidance about birth control measures; lactating women will be ineligible

- Pre-treatment baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
must be assessed

- Patients that are known to have acquired immune deficiency syndrome (AIDS) are
excluded from this trial because the safety of the agents on this population has not
been established

- Participation in E3A93 is mandatory for all patients in E5A93; patients must be
registered separately to each protocol, first to E5A93, then to E3A93; NOTE: Study
participants from South African institutions are exempt from mandatory registration
to E3A93 due to costs and problems associated with international shipping

- Patients must give written informed consent

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median survival

Outcome Description:

Detected using a one-sided log rank test at the .05 significance level.

Outcome Time Frame:

Up to 1 year

Safety Issue:


Principal Investigator

Robert Kyle

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

July 1994

Completion Date:

Related Keywords:

  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Eastern Cooperative Oncology Group Boston, Massachusetts  02215