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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00317811
First received: April 24, 2006
Last updated: November 5, 2013
Last verified: June 2011
  Purpose

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Dietary Supplement: ascorbic acid
Drug: bortezomib
Drug: melphalan
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response rate (complete response [CR], near CR, partial response, and minimal response) [ Designated as safety issue: No ]
  • Safety and tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Proportion of patients responding [ Designated as safety issue: No ]
  • Time to disease progressionin patients receiving maintenance treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival as assessed by the Kaplan-Meier method [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: November 2005
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317811

Locations
United States, California
Hematology-Oncology Medical Group of Fresno, Incorporated
Fresno, California, United States, 93720
Hematology Oncology Medical Group of Orange County, Incorporated
Orange, California, United States, 92868
Oncotherapeutics
West Hollywood, California, United States, 90069
United States, Florida
Florida Cancer Specialists - Bonita Springs
Bonita Springs, Florida, United States, 34135
Florida Oncology Associates
Orange Park, Florida, United States, 32073
United States, Georgia
Atlanta Cancer Care - Roswell
Roswell, Georgia, United States, 30076
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, New York
SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
Sponsors and Collaborators
Oncotherapeutics
Investigators
Principal Investigator: James R. Berenson, MD Oncotherapeutics
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00317811     History of Changes
Other Study ID Numbers: CDR0000479708, ONCOTHER-20052183, ONCOTHER-BAM2005, MILLENNIUM-ONCOTHER-20052183
Study First Received: April 24, 2006
Last Updated: November 5, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Ascorbic Acid
Melphalan
Bortezomib
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014