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A Prospective Study of Bortezomib in Combination With Melphalan and Prednisone for Patients With Previously Untreated Multiple Myeloma

Phase 2
18 Years
Not Enrolling
Multiple Myeloma

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Trial Information

A Prospective Study of Bortezomib in Combination With Melphalan and Prednisone for Patients With Previously Untreated Multiple Myeloma

Based on the need to improve front-line therapy for patients less likely to undergo
transplant, the promising recent in vitro and clinical work on melphalan and bortezomib, we
propose a prospective trial with bortezomib added to standard melphalan and prednisone
therapy for previously untreated patients with multiple myeloma. Bortezomib 1.3 mg/m2 will
be given twice weekly for two weeks and will be added to standard melphalan and prednisone
on a 4-week cycle. This three-drug combination will be compared to historical data. We
have treated 2 patients with relapsed disease following >2 prior regimens including
high-dose therapy with autologous stem cell support. Each patient received melphalan,
prednisone, and bortezomib as described below and both had marked declines in M-protein
within 2 cycles. These responses have been sustained for at least 3 months and treatment
was well tolerated.

Eligible patients will have histologically confirmed Multiple Myeloma (MM) having not
received prior systemic therapy given with the intent to induce remission, be adults, have
life expectancy greater than 3 months, adequate performance status, organ and marrow
function as described in the protocol, not be pregnant, HIV positive, or taking any
investigational agents. Patients must not have history of allergic reactions to study drugs
or similar compounds or have uncontrolled intercurrent illness or social situation that
would limit compliance with study requirements. Patients must also have the ability to give
informed consent.

Study drugs will be administered on an inpatient or outpatient basis. Bortezomib 1.3 mg/m2
is administered intravenously in a 3-5 second bolus on days 1, 4, 8, and 11 of a 28 day
cycle. Six cycles are planned. On days when both melphalan and bortezomib are given,
melphalan is given at least one hour prior to bortezomib. Melphalan 6 mg/m2 is administered
orally on an empty stomach daily on days 1-7 of each cycle. Prednisone 60 mg/m2 is
administered orally daily on days 1-7 of each cycle. Supportive care measures such as
antiemetics and growth factors may be given.

Inclusion Criteria:

- Patients must have histologically confirmed multiple myeloma, defined as at least one
of the following major criteria and one minor criterion or at least three minor

Major Criteria Minor Criteria Plasmacytoma on tissue biopsy Marrow
plasmacytosis 10-29% Marrow plasmacytosis ≥ 30% Monoclonal protein present, less than
major criteria Monoclonal protein: Lytic bone lesions

Immunoglobulin G (IgG) > 3.5 g/dl Decrease in uninvolved immunoglobulins:

Immunoglobulin A (IgA) > 2 g/dl Immunoglobulin M (IgM) < 50 mg/dl Bence Jones ≥ 1
g/24 hr IgA < 100 mg/dl IgG < 600 mg/dl

- No prior therapy

- Life expectancy greater than 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >40%

- Patients must have normal organ and marrow function. Patients with severe
pancytopenia due to myeloma involvement of the bone marrow and patients with renal
insufficiency (creatinine > 2 mg/dl) due to myeloma will also be included.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Pregnant women

- Patients may not be receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bortezomib, melphalan, or other agents used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with bortezomib or other agents administered during the

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Overall response rate equals complete response and partial response per Southwest Oncology Group Criteria. Measurable, quantifiable protein criteria must be present. Acceptable protein criteria are quantitative immunoglobulin IgG, IgA, IgD, IgE or IgM and/or urine M-component (Bence-Jones protein). If both are present, the quantitative immunoglobulin will be followed for response. Complete Remission: The absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-components on electrophoresis as by immunofixation studies. There must also be no evidence of increasing anemia. Partial Remission: A 50-74% reduction in the quantitative immunoglobulin, and if present, a 50-89% reduction in the urine M-component (Bence-Jones protein). Stable/No Remission): A <50% reduction I nthe quantitative immunoglobulin, or if the patient has light-chain disease only, a <50% reduction in the urine M-component (Bence-Jones protein.

Outcome Time Frame:

6 weeks following completion of treatment

Safety Issue:


Principal Investigator

Cristina Gasparetto, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

July 2004

Completion Date:

February 2008

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Duke University Medical CenterDurham, North Carolina  27710