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

Primary Purpose

Stage II Multiple Myeloma, Stage III Multiple Myeloma, Refractory Plasma Cell Neoplasm

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
arsenic trioxide
ascorbic acid
melphalan
chemosensitization/potentiation
chemotherapy
Sponsored by
Oncotherapeutics
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage II Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Palo Verde Hematology Oncology
  • Comprehensive Blood and Cancer Center
  • Southbay Oncology / Hematology Medical Group
  • Hematology-Oncology Medical Group of Fresno, Incorporated
  • Hematology Oncology Medical Group of Orange County, Incorporated
  • Cancer Care Associates Medical Group - Redondo Beach
  • Redwood Regional Oncology Center - Sotoyome
  • Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital
  • San Diego Cancer Center - Vista
  • Oncotherapeutics
  • Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
  • Atlanta Cancer Care - Roswell
  • Tulane Cancer Center at Tulane University Hospital and Clinic
  • Center for Cancer and Blood Disorders at Suburban Hospital
  • William Beaumont Hospital - Royal Oak Campus
  • Hackensack University Medical Center Cancer Center
  • Abramson Cancer Center of the University of Pennsylvania
  • Utah Cancer Specialists - Administrative Office

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
June 10, 2004
Last Updated
July 9, 2013
Sponsor
Oncotherapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00085345
Brief Title
Melphalan, Arsenic Trioxide, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official Title
Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2006
Overall Recruitment Status
Withdrawn
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Oncotherapeutics

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage II Multiple Myeloma, Stage III Multiple Myeloma, Refractory Plasma Cell Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
arsenic trioxide
Intervention Type
Drug
Intervention Name(s)
ascorbic acid
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
chemosensitization/potentiation
Intervention Type
Procedure
Intervention Name(s)
chemotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James R. Berenson, MD
Organizational Affiliation
Oncotherapeutics
Official's Role
Study Chair
Facility Information:
Facility Name
Palo Verde Hematology Oncology
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85304
Country
United States
Facility Name
Comprehensive Blood and Cancer Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309-0633
Country
United States
Facility Name
Southbay Oncology / Hematology Medical Group
City
Campbell
State/Province
California
ZIP/Postal Code
95008
Country
United States
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
Hematology-Oncology Medical Group of Fresno, Incorporated
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Hematology Oncology Medical Group of Orange County, Incorporated
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Cancer Care Associates Medical Group - Redondo Beach
City
Redondo Beach
State/Province
California
ZIP/Postal Code
90277
Country
United States
Facility Name
Redwood Regional Oncology Center - Sotoyome
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95405
Country
United States
Facility Name
Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital
City
Soquel
State/Province
California
ZIP/Postal Code
95073
Country
United States
Facility Name
San Diego Cancer Center - Vista
City
Vista
State/Province
California
ZIP/Postal Code
92083
Country
United States
Facility Name
Oncotherapeutics
City
West Hollywood
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Atlanta Cancer Care - Roswell
City
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
Tulane Cancer Center at Tulane University Hospital and Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112-2699
Country
United States
Facility Name
Center for Cancer and Blood Disorders at Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
William Beaumont Hospital - Royal Oak Campus
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Hackensack University Medical Center Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Abramson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4283
Country
United States
Facility Name
Utah Cancer Specialists - Administrative Office
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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