Antibiotic Therapy in Preventing Early Infection in Patients With Multiple Myeloma Who Are Receiving Chemotherapy

OBJECTIVES:

- Evaluate whether oral antibiotic prophylaxis with co-trimoxazole (TMP-SMX) versus
ciprofloxacin (CPFX) or ofloxacin versus no prophylaxis will significantly reduce rates
of serious bacterial infections during the first 3 months of chemotherapy in patients
with multiple myeloma.

- Determine whether antibiotic prophylaxis with TMP-SMX or CPFX (or ofloxacin) is
associated with an increased incidence of nonbacterial infection or an increased rate
of infection from organisms resistant to prophylactic antibiotics.

- Evaluate whether oral antibiotic prophylaxis with CPFX or ofloxacin is as effective as
TMP-SMX without the associated toxic effects.

- Evaluate whether protection against early infection in multiple myeloma patients can
improve their response to initial chemotherapy.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating
center. Patients are randomized to 1 of 2treatment arms.

- Arm I: Patients receive co-trimoxazole every 12 hours for 2 months followed by
observation for 2 months.

- Arm II: Patients receive oral ciprofloxacin or ofloxacin every 12 hours for 2 months
followed by observation for 1 month.

- Arm III: The patient will receive no prophylaxis.

Patients continue their randomly assigned treatment throughout any infection in addition to
any treatment needed for infection. Patients also remain on their randomly assigned
treatment if chemotherapy is discontinued, changed, or delayed during the 3 month study.

Patients are followed at 6 months, 1 year, and 2 years.

PROJECTED ACCRUAL: A total of 212 patients (71 per treatment arm) will be accrued for this
study.

Inclusion:

- Patient must have a diagnosis of multiple myeloma confirmed by the presence of:

- Bone marrow plasmacytosis with >10% abnormal plasma cells or multiple biopsy-proven
plasmacytomas, and at least one of the criteria below must be documented:

1. Myeloma protein in the serum

2. Myeloma protein in the urine (free monoclonal light chain)

3. Radiologic evidence of osteolytic lesions (generalized osteoporosis qualifies
only if the bone marrow aspirate contains >20% plasma cells)

- Patients must have no active infection during the prior seven days and be off all
antibiotics for the prior seven days.

- Patients cannot have received radiotherapy during the preceding ten days.

- Primary therapy for multiple myeloma must start within three days after entry to this
study. For purposes of eligibility for this study, myelosuppressive chemotherapy or
high-dose dexamethasone based regimens are acceptable as primary therapy. The
high-dose dexamethasone regimen must include, at a minimum, dexamethasone 40 mg per
day days 1-4, 9-12, 17-20 for the first cycle and 40 mg per day on days 1-4 of the
second cycle.

- Patients who are to receive dexamethasone alone or dexamethasone with thalidomide are
among those eligible for this protocol.

- Patients must have a serum creatinine <5.0 mg/dl and not require dialysis at the time
of study entry. If patients require dialysis after enrollment, they can continue on
the protocol using the adjusted medication guidelines

- Written informed consent must be obtained prior to entry.

Exclusion:

- Patients with smoldering myeloma, history of hypersensitivity to fluoroquinolones or
trimethoprim, bone marrow transplant or autologous stem cell rescue planned during the
first two months of treatment, patients taking theophylline, or patients previously
treated with chemotherapy or high-dose dexamethasone