Combination Chemotherapy With or Without PSC 833 in Treating Patients With Relapsed or Refractory Multiple Myeloma

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining PSC 833 with chemotherapy may reduce resistance to the drug, and allow more tumor cells to be killed. It is not yet known whether combination chemotherapy plus PSC 833 is more effective than combination chemotherapy alone in treating patients with relapsed or refractory multiple myeloma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 in treating patients with relapsed or refractory multiple myeloma.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eastern Cooperative Oncology Group
• Collaborators: Cancer and Leukemia Group B; European Organisation for Research and Treatment of Cancer - EORTC; National Cancer Institute (NCI); NCIC Clinical Trials Group; Southwest Oncology Group
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Doxorubicin; Liposomal doxorubicin; Vincristine

Criteria

DISEASE CHARACTERISTICS:

• Multiple myeloma of any stage confirmed by:

• Bone marrow plasmacytosis with at least 10% plasma cells, sheets of plasma cells, or biopsy proven plasmacytosis

• Myeloma (M) protein in serum and/or urine

• Measurable disease by at least one of the following:

• Serum M-component at least 1.0 g/dL by electrophoresis

• Baseline measurement by nephelometry also, if used to follow response

• Urine M-protein excretion greater than 200 mg/24 hours by electrophoresis

• The following are not considered measurable but are followed for response:

• Lytic bone lesions

• Bone marrow plasmacytosis

• Anemia

• Serum beta 2-microglobulin

• Objective evidence of progression by at least one of the following:

• Increased serum M-protein (by electrophoresis unless M-spike less than 1.5 g/dL)

• At least 50% above lowest remission level or by at least 2 g/dL

• To more than 1.0 g/dL if sole protein indication of relapse

• Nephelometry may be used instead of electrophoresis

• Increased urine M-protein

• To 50% above lowest level OR by 2 g/24 hours

• To greater than 200 mg/24 hours

• Definite new lytic bone lesions or at least a 50% increase in size of existing lesions (discussion with ECOG Study Chairman required if sole indication of progression)

• Increase in serum or urine M-protein by 25% to under 50% (as above) plus one of the following:

• Serum calcium greater than 12 mg/dL without other cause

• Hemoglobin decreased by more than 2.0 g/dL not attributed to chemotherapy, interferon therapy, or a myelodysplastic syndrome

• Less than 11 g/dL in men

• Less than 10 g/dL in women

• At least a 50% increase in bone marrow plasmacytosis

• Failure of prior cytotoxic therapy defined by one of the following:

• Never responded

• Relapsed within 2 months of last treatment

• Relapsed 2-12 months after last treatment following initial response

• Adequate prior chemotherapy required, e.g.:

• At least 2 courses of combination chemotherapy (e.g., VBMCP, VBAP, MP)

• Prior vincristine, doxorubicin, and dexamethasone (VAD) allowed

• No demonstrated resistance to VAD

• At least 3 months since prior VAD

• Cumulative doxorubicin dose no more than 250 mg/m2

• Prior autologous peripheral blood stem cell transplant allowed if performed prior to development of drug resistance

• No prior allogeneic transplant

• No smoldering myeloma, localized plasmacytoma, or monoclonal gammopathy of undetermined significance (MGUS)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• AST less than 1.5 times ULN

• No chronic or active hepatitis or cirrhosis

Renal:

• Creatinine less than 3.0 mg/dL

Cardiovascular:

• Ejection fraction at least 50%

• No history of congestive heart failure

• No overt angina despite medication

• No myocardial infarction within 2 months

• No poorly controlled hypertension (i.e., pressure 200/110 or higher despite medication)

• No arrhythmia requiring therapy (i.e., sustained atrial or ventricular arrhythmia or multifocal premature ventricular contraction)

• Digoxin to control ventricular rate of atrial fibrillation that has been chronic for more than 1 month allowed

Neurologic:

• No peripheral neuropathy with weakness

• No cerebellar disease with ataxia

Gastrointestinal:

• Adequate gastrointestinal function to allow absorption of PSC 833

• No active peptic ulcer

Other:

• No hypersensitivity to PSC 833 or cyclosporine

• No active infection

• HIV negative

• No uncontrolled diabetes mellitus

• No second malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other localized cancer treated with surgery alone

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other serious medical problem unless sufficiently stabilized

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy (e.g., interferon) allowed

Chemotherapy:

• See Disease Characteristics

• At least 3 weeks since other prior chemotherapy (including plicamycin)

Endocrine therapy:

• At least 2 weeks since high dose steroids (at least 100 mg/m2/day of prednisone or at least 40 mg/day of dexamethasone (including steroids for hypercalcemia)

Radiotherapy:

• At least 2 weeks since prior radiotherapy except limited radiotherapy to a single bone lesion

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No concurrent anticoagulants

• No concurrent drugs known to modulate cyclosporine blood concentrations