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

Oral Antibiotic Prophylaxis of Early Infection in Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Infection
• Intervention / Treatment: Drug: ciprofloxacin; Drug: ofloxacin; Drug: 160 mg trimethoprim and 800 mg sulfamethoxazole

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.

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 3

Contacts and Locations

Study Locations

• Peru
  • Lima, Peru, Lima 34
    • Instituto Nacional de Enfermedades Neoplasicas
• South Africa
  • Pretoria, South Africa, 0001
    • Pretoria Academic Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
    • Mobile, Alabama, United States, 36606
      • MBCCOP - Gulf Coast
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Ottumwa, Iowa, United States, 52501
      • McCreery Cancer Center at Ottumwa Regional
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • St. Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Regional Cancer Center at Hunterdon Medical Center
    • Phillipsburg, New Jersey, United States, 08865
      • Warren Hospital
  • New York
    • Bronx, New York, United States, 10466
      • Our Lady of Mercy Medical Center Comprehensive Cancer Center
    • East Syracuse, New York, United States, 13057
      • CCOP - Hematology-Oncology Associates of Central New York
    • New York, New York, United States, 10011
      • St. Vincent's Comprehensive Cancer Center - Manhattan
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
  • Ohio
    • Canton, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center at MetroHealth Medical Center
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Clinic Research Foundation
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ciprofloxacin or ofloxacin; Quinolone: Ciprofloxacin 500 mg every 12 hours or Ofloxacin400 mg every 12 hours.	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.; Other Names: Cipro; Drug: 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.; Other Names: Floxin
Experimental: TMP-SMX; TMP-SMX: 160 mg trimethoprim and 800 mg sulfamethoxazole every 12 hours	Drug: 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..; Other Names: Bactrim; Septra; TMP-SMX
No Intervention: No prophylaxis; The patient will receive no prophylactic antibiotics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Gary Morrow
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group
• Investigators: Study Chair: Gary R. Morrow, PhD, MS, University of Rochester; Study Chair: Martin M. Oken, MD, CCOP - Metro-Minnesota; Study Chair: Claire Pomeroy, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start: March 1, 1997
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): November 11, 2015
• Last Update Submitted That Met QC Criteria: October 13, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: infection; stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Ciprofloxacin; Ofloxacin; Trimethoprim; Sulfamethoxazole
• Other Study ID Numbers: CDR0000065093; U10CA037420 (U.S. NIH Grant/Contract); URCC-U10994 (Other Identifier: University of Rochester Cancer Center); NCI-C95-0001 (Other Identifier: NIH/NCI DCP); URCC-URRSRB-6993 (Other Identifier: University of Rochester IRB); NCI-P96-0073 (Other Identifier: NCI); ECOG-U1099 (Other Identifier: ECOG)