Melphalan, Arsenic Trioxide, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma
Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Plasma Cell Neoplasm
Intervention: arsenic trioxide (Drug); ascorbic acid (Drug); melphalan (Drug); chemosensitization/potentiation (Procedure); chemotherapy (Procedure)
Phase: Phase 2
Status: Withdrawn
Sponsored by: Oncotherapeutics Official(s) and/or principal investigator(s): James R. Berenson, MD, Study Chair, Affiliation: Oncotherapeutics
Summary
RATIONALE: Drugs used in chemotherapy, such as melphalan, arsenic trioxide, and ascorbic
acid, work in different ways to stop cancer cells from dividing so they stop growing or die.
Arsenic trioxide and ascorbic acid may also help melphalan kill more cancer cells by making
them more sensitive to the drugs.
PURPOSE: This phase II trial is studying how well giving melphalan together with arsenic
trioxide and ascorbic acid works in treating patients with relapsed or refractory multiple
myeloma.
Clinical Details
Official title: Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma
Study design: Primary Purpose: Treatment
Detailed description:
OBJECTIVES:
Primary
- Determine the time to progression in patients with relapsed or refractory multiple
myeloma (MM) treated with melphalan, arsenic trioxide, and ascorbic acid.
- Determine the response rate (combined complete response, partial response, and minimal
response) in patients treated with this regimen.
- Determine the safety and tolerability of this regimen in these patients.
Secondary
- Determine the time to response and overall survival of patients treated with this
regimen.
- Determine the effects of this regimen on renal failure associated with MM in these
patients.
OUTLINE: This is an open-label, non-randomized, multicenter study.
Patients receive oral melphalan once daily on days 1-4 of week 1 and arsenic trioxide (ATO)
IV over 1-2 hours and ascorbic acid IV over 15 minutes on days 1-4 of week 1 and then twice
weekly during weeks 2-5. Treatment repeats every 6 weeks for up to 6 courses in the absence
of disease progression or unacceptable toxicity. Patients with disease progression any time
after course 1 also receive oral prednisone once daily on days 1-4 and 22-25 of each course.
Patients achieving a complete response after 6 courses of therapy undergo bone marrow biopsy
and receive no further therapy. Patients achieving stable disease or a partial response
after 6 courses of therapy continue to receive ATO and ascorbic acid once weekly.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma meeting at least 1 of the following criteria:
- Relapsed disease after a response to standard first-line chemotherapy (e. g.,
vincristine, doxorubicin, and dexamethasone [VAD] OR melphalan and prednisone) or
first-line high-dose chemotherapy
- Refractory disease (failed to achieve at least stable disease) to most recent
chemotherapy with or without systemic corticosteroids
- 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
- No non-secretory myeloma
- No plasma cell leukemia
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- Platelet count ≥ 50,000/mm^3 (30,000/mm^3 if bone marrow is extensively infiltrated)
- Hemoglobin ≥ 8. 0 g/dL
- Absolute neutrophil count ≥ 1,000/mm^3
- Pancytopenia secondary to multiple myeloma or hypersplenism allowed
Hepatic
- AST and ALT ≤ 3 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN (unless clearly related to disease)
- No known active hepatitis B or C infection
Renal
- Calcium < 14 mg/dL
Cardiovascular
- No evidence of acute ischemia or new conduction system abnormality by
electrocardiogram
- No myocardial infarction within the past 6 months
- No New York Heart Association class III or IV heart failure
- No poorly controlled hypertension
- No prolonged corrected QT interval (> 460 ms) with potassium > 4 mmol/L and magnesium
≥ 1. 8 mmol/L
Other
- No active infection
- No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes)
- No diabetes mellitus
- No other serious medical or psychiatric illness that would preclude study
participation
- No known allergic reaction attributable to compounds of similar chemical or
biological composition to study drugs
- No history of grand mal seizures
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior immunotherapy or antibody therapy
Chemotherapy
- See Disease Characteristics
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
Endocrine therapy
- See Disease Characteristics
- No other concurrent corticosteroids
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- More than 4 weeks since prior major surgery
Other
- No other concurrent investigational agents
Locations and Contacts
Palo Verde Hematology Oncology, Glendale, Arizona 85304, United States
Comprehensive Blood and Cancer Center, Bakersfield, California 93309-0633, United States
Southbay Oncology / Hematology Medical Group, Campbell, California 95008, United States
Fountain Valley, California 92708, United States
Hematology-Oncology Medical Group of Fresno, Incorporated, Fresno, California 93720, United States
Hematology Oncology Medical Group of Orange County, Incorporated, Orange, California 92868, United States
Cancer Care Associates Medical Group - Redondo Beach, Redondo Beach, California 90277, United States
Redwood Regional Oncology Center - Sotoyome, Santa Rosa, California 95405, United States
Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital, Soquel, California 95073, United States
San Diego Cancer Center - Vista, Vista, California 92083, United States
Oncotherapeutics, West Hollywood, California 90069, United States
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center, Miami Beach, Florida 33140, United States
Atlanta Cancer Care - Roswell, Roswell, Georgia 30076, United States
Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans, Louisiana 70112-2699, United States
Center for Cancer and Blood Disorders at Suburban Hospital, Bethesda, Maryland 20817, United States
William Beaumont Hospital - Royal Oak Campus, Royal Oak, Michigan 48073, United States
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States
Utah Cancer Specialists - Administrative Office, Salt Lake City, Utah 84106, United States
Additional Information
Last updated: July 9, 2013
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