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

• ClinicalTrials.gov Identifier: NCT00002850
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: February 13, 2015
• Last Update Posted: November 11, 2015
• Sponsor: Gary Morrow
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group
• Information provided by (Responsible Party): Gary Morrow, University of Rochester NCORP Research Base

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infection; Multiple Myeloma	Drug: ciprofloxacin; Drug: ofloxacin; Drug: 160 mg trimethoprim and 800 mg sulfamethoxazole	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Oral Antibiotic Prophylaxis of Early Infection in Multiple Myeloma
• Study Start Date: March 1997
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: January 2012

Arms and Interventions

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 Name: 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 Name: 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: TMP-SMX; Septra; Bactrim
No Intervention: No prophylaxis; The patient will receive no prophylactic antibiotics.

Outcome Measures

Primary Outcome Measures :

1. Proportion of Patients Experiencing a Serious Bacterial Infection [ Time Frame: First three months of chemotherapy ]
   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.

Eligibility Criteria

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

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

Contacts and Locations

  Show 45 Study Locations

Sponsors and Collaborators

Gary Morrow

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

More Information

• Responsible Party: Gary Morrow, Director, UR NCORP Research BAase, University of Rochester NCORP Research Base
• ClinicalTrials.gov Identifier: NCT00002850 History of Changes
• 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 )
• First Posted: January 27, 2003
• Results First Posted: February 13, 2015
• Last Update Posted: November 11, 2015
• Last Verified: October 2015

Keywords provided by Gary Morrow, University of Rochester NCORP Research Base:

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; infection

Additional relevant MeSH terms:

Infection; Communicable Diseases; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Anti-Bacterial Agents; Ciprofloxacin; Ofloxacin; Levofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Antibiotics, Antitubercular; Trimethoprim; Sulfamethoxazole; Anti-Infective Agents; Antitubercular Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action