A Phase II Trial of Bortezomib + Ascorbic Acid + Melphalan (BAM) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
A Phase II Trial of Bortezomib + Ascorbic Acid + Melphalan (BAM) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma
OBJECTIVES:
Primary
- Determine the overall response rate (combined complete response [CR], near CR, partial
response [PR], and minimal response [MR]) and time to progression of disease in
patients with newly diagnosed multiple myeloma treated with bortezomib, ascorbic acid,
and melphalan.
- Assess the safety and tolerability of this regimen in these patients.
Secondary
- Assess the time to response in these patients.
- Determine progression-free and overall survival of these patients.
- Assess time to disease progression among subjects who continue to maintenance treatment
with bortezomib.
OUTLINE: This is an open-label study.
- Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral
melphalan and oral ascorbic acid on days 1-4. Treatment repeats every 28 days to
maximum response [MR] or for at least 8 courses in the absence of disease progression
or unacceptable toxicity. Patients with responding disease receive an additional 2
courses of induction therapy beyond MR and proceed to maintenance therapy. Patients
with stable disease or without a maximum reduction in their paraprotein after 8 courses
of induction therapy are eligible to receive maintenance therapy.
- Maintenance therapy: Patients receive bortezomib IV on days 1 and 15. Treatment repeats
every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Newly diagnosed symptomatic multiple myeloma based on the following criteria:
- Durie-Salmon staging
- Measurable disease, defined as a monoclonal immunoglobulin spike on serum
electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥
200 mg/24 hours
- Symptomatic disease
- No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein [M-protein], and skin changes)
- No plasma cell leukemia
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Life expectancy > 3 months
- Platelet count ≥ 50,000/mm³ (30,000/mm³ if the bone marrow is extensively
infiltrated)
- Hemoglobin ≥ 8.0 g/dL
- Absolute neutrophil count ≥ 1,000/mm³
- Creatinine ≤ 3 mg/dL
- Sodium > 130 mmol/L corrected
- AST and ALT ≤ 3 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN unless clearly related to the disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Any ECG abnormality has to be documented by the investigator as not medically
relevant
- No electrocardiographic evidence of acute ischemia or new conduction system
abnormalities
- No myocardial infarction or EKG evidence of infarction within the past 6 months
- No active infection
- No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L])
- No New York Heart Association class III or IV heart failure
- No uncontrolled angina
- No severe uncontrolled ventricular arrhythmias
- No active conduction system abnormalities
- No poorly controlled hypertension
- No diabetes mellitus
- No known HIV infection
- No known active hepatitis B or C viral infection
- No history of grand mal seizures
- No history of allergic reaction to compounds of similar chemical or biological
composition to melphalan, bortezomib, boron, or mannitol
- No peripheral neuropathy ≥ grade 2 within the past 14 days
- No other serious medical or psychiatric illness that could potentially interfere with
the completion of study treatment
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy
- More than 4 weeks since prior major surgery
- No prior therapy for myeloma
- Prior prednisone at a total of 400mg over ≤ 4 days (or an equivalent potency of
another steroid) allowed
- No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent)
- No other concurrent investigational agents
- No other concurrent antimyeloma therapy
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall response rate (complete response [CR], near CR, partial response, and minimal response)
Safety Issue:
No
Principal Investigator
James R. Berenson, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Oncotherapeutics
Authority:
United States: Federal Government
Study ID:
CDR0000479708
NCT ID:
NCT00317811
Start Date:
November 2005
Completion Date:
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| SUNY Downstate Medical Center | Brooklyn, New York 11203 |
| Florida Oncology Associates | Orange Park, Florida 32073 |
| Oncotherapeutics | Los Angeles, California 90067 |
| Hematology-Oncology Medical Group of Fresno, Incorporated | Fresno, California 93720 |
| Hematology Oncology Medical Group of Orange County, Incorporated | Orange, California 92868 |
| Atlanta Cancer Care - Roswell | Roswell, Georgia 30076 |
| Florida Cancer Specialists - Bonita Springs | Bonita Springs, Florida 34135 |
