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Stage I Multiple MyelomaPhase 3NCT00002556

Combination Chemotherapy With or Without High Dose Cyclophosphamide and Recombinant Interferon Alfa-2b in Treating Patients With Previously Untreated Stage I-III Multiple Myeloma

A Phase 3 study testing vincristine sulfate, carmustine and melphalan in people with Stage I Multiple Myeloma and Stage II Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase III clinical trial studies combination chemotherapy with high dose cyclophosphamide and recombinant interferon alfa-2b to see how well it works compared to combination chemotherapy alone in treating patients with previously untreated stage I-III multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vincristine sulfate, carmustine and melphalan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
312 participants
Where
1 siteUnited States
Study dates
Jul 1994to Jan 2006
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 36Show fewer
  • 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 electrophoresis
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: 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

This randomized phase III clinical trial studies combination chemotherapy with high dose cyclophosphamide and recombinant interferon alfa-2b to see how well it works compared to combination chemotherapy alone in treating patients with previously untreated stage I-III multiple myeloma. Drugs used in chemotherapy, such as vincristine sulfate, carmustine, melphalan, cyclophosphamide, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of cancer cells. It is not yet know whether giving combination chemotherapy with or without alternating high-dose cyclophosphamide and recombinant interferon alfa-2b is more effective in treating multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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 survival.

OUTLINE:

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.

Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • carmustineDrug

    Also called BCNU, BiCNU, bis-chloronitrosourea

    Given IV

  • melphalanDrug

    Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard

    Given PO

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given PO

  • recombinant interferon alfa-2bBiological

    Also called Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00002556
Study groupRoleWhat they receive
ARM A (VBMCP)Active comparatorINDUCTION PHASE: Patients receive VBMCP comprising vincristine sulfate IV on day 1, carmustine IV on day 1, melphalan 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 receive VBMCP as in the induction phase. Courses repeat every 35 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: vincristine sulfate; Drug: carmustine; Drug: melphalan; Drug: cyclophosphamide; Drug: prednisone; Other: laboratory biomarker analysis
Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)ExperimentalINDUCTION PHASE: Patients receive VBMCP comprising vincristine sulfate IV on day 1, carmustine IV on day 1, melphalan 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 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 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.
Receives: Drug: vincristine sulfate; Drug: carmustine; Drug: melphalan; Drug: cyclophosphamide; Drug: prednisone; Biological: recombinant interferon alfa-2b; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median survival

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

    Measured: Up to 1 year

  2. Objective response, evaluated using the following ECOG Myeloma Response Criteria

    Compared between treatment groups using a two-sided Fisher Exact Test at the .05 significance level. Response evaluation will be based on determination of reduction in serum and/or urine M-protein (monoclonal or myeloma protein) and on improvement in measurable soft tissue plasmacytomas when present.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJul 1994
  3. Primary completionJan 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
312 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00002556
Sponsor's protocol ID
NCI-2012-02445
Other IDs
E5A93, ECOG-E5A93, U10CA021115
Status last verified
May 2013
First submitted
1 Nov 1999
Last updated
31 May 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing vincristine sulfate, carmustine and melphalan in people with Stage I Multiple Myeloma and Stage II Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median survival (time frame: Up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00002556.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2013.

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