Bortezomib, Ascorbic Acid, and Melphalan in Treating Patients With Newly Diagnosed Multiple Myeloma

Sponsor

Oncotherapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00317811

Collaborator

(none)

Enrollment

Locations

4.4

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ascorbic acid may help melphalan work better by making cancer cells more sensitive to the drug. Giving bortezomib together with ascorbic acid and melphalan may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with ascorbic acid and melphalan works in treating patients with newly diagnosed multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Dietary Supplement: ascorbic acid Drug: bortezomib Drug: melphalan	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Bortezomib + Ascorbic Acid + Melphalan (BAM) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Feb 1, 2009

Outcome Measures

Primary Outcome Measures

Overall response rate (complete response [CR], near CR, partial response, and minimal response) []
Safety and tolerability as assessed by NCI CTCAE v3.0 []
Proportion of patients responding []
Time to disease progressionin patients receiving maintenance treatment []

Secondary Outcome Measures

Time to response []
Progression-free survival []
Overall survival as assessed by the Kaplan-Meier method []
Time to disease progression []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology-Oncology Medical Group of Fresno, Incorporated	Fresno	California	United States	93720
2	Hematology Oncology Medical Group of Orange County, Incorporated	Orange	California	United States	92868
3	Oncotherapeutics	West Hollywood	California	United States	90069
4	Florida Cancer Specialists - Bonita Springs	Bonita Springs	Florida	United States	34135
5	Florida Oncology Associates	Orange Park	Florida	United States	32073
6	Atlanta Cancer Care - Roswell	Roswell	Georgia	United States	30076
7	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
8	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203