Melphalan, Arsenic Trioxide, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma

Stage III Multiple Myeloma Clinical Trial

Official title:

Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00085345
• Other study ID #: ONCOTHER-MAC001
• Secondary ID: CDR0000368637
• Status: Withdrawn
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: July 9, 2013

Study information

• Verified date: July 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasmacytoma
• Refractory Plasma Cell Neoplasm
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• arsenic trioxide

• ascorbic acid

• melphalan

Procedure:
• chemosensitization/potentiation

• chemotherapy

Locations

Country	Name	City	State
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Center for Cancer and Blood Disorders at Suburban Hospital	Bethesda	Maryland
United States	Southbay Oncology / Hematology Medical Group	Campbell	California
United States	Hematology-Oncology Medical Group of Fresno, Incorporated	Fresno	California
United States	Palo Verde Hematology Oncology	Glendale	Arizona
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center	Miami Beach	Florida
United States	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Hematology Oncology Medical Group of Orange County, Incorporated	Orange	California
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Cancer Care Associates Medical Group - Redondo Beach	Redondo Beach	California
United States	Atlanta Cancer Care - Roswell	Roswell	Georgia
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Utah Cancer Specialists - Administrative Office	Salt Lake City	Utah
United States	Redwood Regional Oncology Center - Sotoyome	Santa Rosa	California
United States	Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital	Soquel	California
United States	San Diego Cancer Center - Vista	Vista	California
United States	Oncotherapeutics	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Oncotherapeutics

Country where clinical trial is conducted

United States,