NCT00002556

Brief 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. 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
312

participants targeted

Target at P50-P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 1994

Completed
5.3 years until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
3.2 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2006

Completed
Last Updated

May 31, 2013

Status Verified

May 1, 2013

Enrollment Period

11.5 years

First QC Date

November 1, 1999

Last Update Submit

May 30, 2013

Conditions

Outcome Measures

Primary Outcomes (2)

  • Median survival

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

    Up to 1 year

  • 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.

    Up to 1 year

Study Arms (2)

ARM A (VBMCP)

ACTIVE COMPARATOR

INDUCTION 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.

Drug: vincristine sulfateDrug: carmustineDrug: melphalanDrug: cyclophosphamideDrug: prednisoneOther: laboratory biomarker analysis

Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

EXPERIMENTAL

INDUCTION 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.

Drug: vincristine sulfateDrug: carmustineDrug: melphalanDrug: cyclophosphamideDrug: prednisoneBiological: recombinant interferon alfa-2bOther: laboratory biomarker analysis

Interventions

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS
ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Given IV

Also known as: BCNU, BiCNU, bis-chloronitrosourea
ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Given PO

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Given PO

Also known as: DeCortin, Deltra
ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Given SC

Also known as: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Intron A
Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Correlative studies

ARM A (VBMCP)Arm B (VBMCP, high dose cyclophosphamide, r alpha 2b IFN)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 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
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

VincristineCarmustineMelphalanCyclophosphamidePrednisoneIntrons

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Vinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesNitrosourea CompoundsUreaAmidesOrganic ChemicalsNitroso CompoundsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsPhosphoramide MustardsPhosphoramidesOrganophosphorus CompoundsPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsDNA, IntergenicGenome ComponentsGenomeGenetic StructuresGenetic PhenomenaGene ComponentsGenes

Study Officials

  • Robert Kyle

    Eastern Cooperative Oncology Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 1999

First Posted

January 27, 2003

Study Start

July 1, 1994

Primary Completion

January 1, 2006

Last Updated

May 31, 2013

Record last verified: 2013-05

Locations