Infection, Multiple Myeloma
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, infection
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.
Interventions
DRUGciprofloxacin
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.
DRUGofloxacin
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.
DRUG160 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..
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Gary Morrow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Experiencing a Serious Bacterial Infection | 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. |
Countries
Peru, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin or Ofloxacin 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. | 69 |
| TMP-SMX trimethoprim-sulfamethoxazole: Begin oral Trimethoprim-sulfamethoxazole 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.. | 76 |
| Observation No prophylaxis: The patient will receive no prophylactic antibiotics. | 67 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Observation | Ciprofloxacin or Ofloxacin | TMP-SMX |
|---|---|---|---|---|
| Age, Continuous | 63.2 years | 65.0 years | 63.7 years | 62.6 years |
| Chemotherapy regimen Melphalan, Prednisone | 34 participants | 10 participants | 11 participants | 13 participants |
| Chemotherapy regimen Other | 93 participants | 27 participants | 28 participants | 38 participants |
| Chemotherapy regimen VBMCP | 22 participants | 8 participants | 6 participants | 8 participants |
| Chemotherapy regimen Vincristine, Adriamycin, Dexamethasone | 63 participants | 22 participants | 24 participants | 17 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status | 1.0 units on a scale | 0.8 units on a scale | 1.0 units on a scale | 1.1 units on a scale |
| Infection in last 6 months Unknown | 184 participants | 59 participants | 56 participants | 69 participants |
| Infection in last 6 months Yes | 28 participants | 8 participants | 13 participants | 7 participants |
| Race/Ethnicity, Customized Unknown | 52 participants | 12 participants | 15 participants | 25 participants |
| Race/Ethnicity, Customized White | 160 participants | 55 participants | 54 participants | 51 participants |
| Region of Enrollment United States | 212 participants | 67 participants | 69 participants | 76 participants |
| Sex: Female, Male Female | 79 Participants | 24 Participants | 23 Participants | 32 Participants |
| Sex: Female, Male Male | 133 Participants | 43 Participants | 46 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 69 | 1 / 76 | 0 / 67 |
| serious Total, serious adverse events | 1 / 69 | 2 / 76 | 0 / 67 |
Outcome results
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.
Time frame: First three months of chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ciprofloxacin or Ofloxacin | Proportion of Patients Experiencing a Serious Bacterial Infection | 12.5 percentage of participants |
| TMP-SMX | Proportion of Patients Experiencing a Serious Bacterial Infection | 6.8 percentage of participants |
| No Prophylaxis | Proportion of Patients Experiencing a Serious Bacterial Infection | 15.9 percentage of participants |
Comparison: H0: There is no significant difference in the incidence of severe bacterial infections among all three arms during the first 2 months of treatment at the two-sided 0.05 significance level.~Ha: There is a significant difference in the incidence of severe bacterial infections among all three arms during the first 2 months of treatment at the two-sided 0.05 significance level.p-value: 0.218Fisher Exact