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

Multiple Myeloma Clinical Trial

Official title:

Oral Antibiotic Prophylaxis of Early Infection in Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002850
• Other study ID #: CDR0000065093
• Secondary ID: U10CA037420URCC-
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: October 13, 2015
• Start date: March 1997
• Est. completion date: January 2012

Study information

• Verified date: October 2015
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: January 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• ciprofloxacin
Begin oral ciprofloxacin when they start chemotherapy for multiple myeloma. Assigned treatment consists of ciprofloxacin (Cipro 500 mg po tablet every 12 hours for two months. The patient will continue to be observed one additional month on study continuing regular myeloma chemotherapy.
• ofloxacin
Begin oral ofloxacin when they start chemotherapy for multiple myeloma. Assigned treatment consists of ofloxacin (500 mg po tablet every 12 hours for two months. The patient will continue to be observed one additional month on study continuing regular myeloma chemotherapy.
• 160 mg trimethoprim and 800 mg sulfamethoxazole
Begin oral TMP-SMX when they start chemotherapy for multiple myeloma. Assigned treatment consists of TMP-SMX (Septra® or Bactrim®) 1 DS tablet [TMP-SMX DS = 160 mg trimethoprim and 800 mg sulfamethoxazole] every 12 hours for two months..

Locations

Country	Name	City	State
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
South Africa	Pretoria Academic Hospital	Pretoria
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	CCOP - Greenville	Greenville	South Carolina
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Warren Hospital	Phillipsburg	New Jersey
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Metro-Minnesota	St. Louis Park	Minnesota
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	CCOP - Northwest	Tacoma	Washington
United States	Chester County Hospital	West Chester	Pennsylvania
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Gary Morrow	Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Experiencing a Serious Bacterial Infection	This study evaluated the impact of prophylactic antibiotics on the incidence of serious bacterial infections (SBIs) during the first 2 months of treatment in patients with newly diagnosed multiple myeloma. Patients with multiple myeloma receiving initial chemotherapy were randomized on a 1:1:1 basis to daily ciprofloxacin, trimethoprim-sulfamethoxazole, or observation and evaluated for SBI for the first 2 months of treatment.	First three months of chemotherapy	No