Clinical trial NCT00002850: Antibiotic Therapy in Preventing Early Infection in Patients With Multiple Myeloma Who Are Receiving Chemotherapy
Official title: Oral Antibiotic Prophylaxis of Early Infection in Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infection
Multiple Myeloma
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
infection
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Giving antibiotics may be effective in preventing or controlling early infection in patients with multiple myeloma and may improve their response to chemotherapy.

PURPOSE: This randomized clinical trial is studying antibiotics to see how well they work compared to no antibiotics in preventing early infection in patients with multiple myeloma.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients Experiencing a Serious Bacterial Infection
timeFrame: First three months of chemotherapy
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MBCCOP - Gulf Coast
state: Alabama
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Ottumwa
country: United States
facility: McCreery Cancer Center at Ottumwa Regional
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: St. Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Flemington
country: United States
facility: Hunterdon Regional Cancer Center at Hunterdon Medical Center
state: New Jersey
city: Phillipsburg
country: United States
facility: Warren Hospital
state: New Jersey
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: New York
country: United States
facility: St. Vincent's Comprehensive Cancer Center - Manhattan
state: New York
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Canton
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital
Study officials:
affiliation: University of Rochester
name: Gary R. Morrow, PhD, MS
role: STUDY_CHAIR
affiliation: CCOP - Metro-Minnesota
name: Martin M. Oken, MD
role: STUDY_CHAIR
affiliation: University of California, Davis
name: Claire Pomeroy, MD
role: STUDY_CHAIR
References: