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

Sponsor

Oncotherapeutics (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00085345

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Primary Purpose:

Treatment

Official Title:

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palo Verde Hematology Oncology	Glendale	Arizona	United States	85304
2	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309-0633
3	Southbay Oncology / Hematology Medical Group	Campbell	California	United States	95008
4		Fountain Valley	California	United States	92708
5	Hematology-Oncology Medical Group of Fresno, Incorporated	Fresno	California	United States	93720
6	Hematology Oncology Medical Group of Orange County, Incorporated	Orange	California	United States	92868
7	Cancer Care Associates Medical Group - Redondo Beach	Redondo Beach	California	United States	90277
8	Redwood Regional Oncology Center - Sotoyome	Santa Rosa	California	United States	95405
9	Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital	Soquel	California	United States	95073
10	San Diego Cancer Center - Vista	Vista	California	United States	92083
11	Oncotherapeutics	West Hollywood	California	United States	90069
12	Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
13	Atlanta Cancer Care - Roswell	Roswell	Georgia	United States	30076
14	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112-2699
15	Center for Cancer and Blood Disorders at Suburban Hospital	Bethesda	Maryland	United States	20817
16	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
17	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
18	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
19	Utah Cancer Specialists - Administrative Office	Salt Lake City	Utah	United States	84106