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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00085345
First received: June 10, 2004
Last updated: July 9, 2013
Last verified: July 2006
  Purpose

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.


Condition Intervention Phase
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Refractory Plasma Cell Neoplasm
Drug: arsenic trioxide
Drug: ascorbic acid
Drug: melphalan
Procedure: chemosensitization/potentiation
Procedure: chemotherapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


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

Enrollment: 0
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00085345

Locations
United States, Arizona
Palo Verde Hematology Oncology
Glendale, Arizona, United States, 85304
United States, California
Comprehensive Blood and Cancer Center
Bakersfield, California, United States, 93309-0633
Southbay Oncology / Hematology Medical Group
Campbell, California, United States, 95008
Fountain Valley, California, United States, 92708
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
Cancer Care Associates Medical Group - Redondo Beach
Redondo Beach, California, United States, 90277
Redwood Regional Oncology Center - Sotoyome
Santa Rosa, California, United States, 95405
Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital
Soquel, California, United States, 95073
San Diego Cancer Center - Vista
Vista, California, United States, 92083
Oncotherapeutics
West Hollywood, California, United States, 90069
United States, Florida
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Georgia
Atlanta Cancer Care - Roswell
Roswell, Georgia, United States, 30076
United States, Louisiana
Tulane Cancer Center at Tulane University Hospital and Clinic
New Orleans, Louisiana, United States, 70112-2699
United States, Maryland
Center for Cancer and Blood Disorders at Suburban Hospital
Bethesda, Maryland, United States, 20817
United States, Michigan
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, United States, 48073
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Utah
Utah Cancer Specialists - Administrative Office
Salt Lake City, Utah, United States, 84106
Sponsors and Collaborators
Oncotherapeutics
Investigators
Study Chair: James R. Berenson, MD Oncotherapeutics
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00085345     History of Changes
Other Study ID Numbers: ONCOTHER-MAC001, CDR0000368637
Study First Received: June 10, 2004
Last Updated: July 9, 2013
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on October 23, 2014