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

• Sponsor: Gary Morrow (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002850
• Collaborator: National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other)
• Enrollment: 212
• Locations: 45
• Arms: 3
• Duration (Months): 178
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0

Study Details

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
• 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: Mar 1, 1997
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Jan 1, 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 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: 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 [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

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36606
2	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36652-2144
3	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
4	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
5	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
6	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
7	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
8	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
11	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
12	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
13	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
14	CCOP - Metro-Minnesota	St. Louis Park	Minnesota	United States	55416
15	CCOP - Kansas City	Kansas City	Missouri	United States	64131
16	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey	United States	08822
17	Warren Hospital	Phillipsburg	New Jersey	United States	08865
18	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York	United States	10466
19	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
20	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York	United States	10011
21	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
22	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
23	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
24	CCOP - Columbus	Columbus	Ohio	United States	43215
25	CCOP - Dayton	Dayton	Ohio	United States	45429
26	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
27	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
28	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
29	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
30	Chester County Hospital	West Chester	Pennsylvania	United States	19380
31	CCOP - Greenville	Greenville	South Carolina	United States	29615
32	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
33	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
34	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
35	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
36	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
37	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
38	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
39	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
40	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
41	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
42	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
43	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
44	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	Lima 34
45	Pretoria Academic Hospital	Pretoria		South Africa	0001

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary Morrow, Director, UR NCORP Research BAase, University of Rochester NCORP Research Base
• ClinicalTrials.gov Identifier: NCT00002850
• Other Study ID Numbers: CDR0000065093; U10CA037420; URCC-U10994; NCI-C95-0001; URCC-URRSRB-6993; NCI-P96-0073; ECOG-U1099
• First Posted: Jan 27, 2003
• Last Update Posted: Nov 11, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Gary Morrow, Director, UR NCORP Research BAase, University of Rochester NCORP Research Base: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; infection
• Additional relevant MeSH terms: Infections; Communicable Diseases; Multiple Myeloma; Neoplasms, Plasma Cell; Ciprofloxacin; Ofloxacin; Trimethoprim; Sulfamethoxazole

Study Results

Participant Flow

Arm/Group Title	Ciprofloxacin or Ofloxacin	TMP-SMX	Observation
Arm/Group Description	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.	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..	Patients observed without intervention and evaluated for SBI for the first 2 months of treatment.
Period Title: Overall Study
STARTED	69	76	67
COMPLETED	64	74	63
NOT COMPLETED	5	2	4

Baseline Characteristics

Arm/Group Title	Ciprofloxacin or Ofloxacin	TMP-SMX	Observation	Total
Arm/Group Description	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.	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..	No prophylaxis: The patient will receive no prophylactic antibiotics.	Total of all reporting groups
Overall Participants	69	76	67	212
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	63.7	62.6	65.0	63.2
Sex: Female, Male (Count of Participants)
Female	23 33.3%	32 42.1%	24 35.8%	79 37.3%
Male	46 66.7%	44 57.9%	43 64.2%	133 62.7%
Race/Ethnicity, Customized (participants) [Number]
White	54 78.3%	51 67.1%	55 82.1%	160 75.5%
Unknown	15 21.7%	25 32.9%	12 17.9%	52 24.5%
Region of Enrollment (participants) [Number]
United States	69 100%	76 100%	67 100%	212 100%
Infection in last 6 months (participants) [Number]
Yes	13 18.8%	7 9.2%	8 11.9%	28 13.2%
Unknown	56 81.2%	69 90.8%	59 88.1%	184 86.8%
Chemotherapy regimen (participants) [Number]
Melphalan, Prednisone	11 15.9%	13 17.1%	10 14.9%	34 16%
VBMCP	6 8.7%	8 10.5%	8 11.9%	22 10.4%
Vincristine, Adriamycin, Dexamethasone	24 34.8%	17 22.4%	22 32.8%	63 29.7%
Other	28 40.6%	38 50%	27 40.3%	93 43.9%
Eastern Cooperative Oncology Group (ECOG) performance status (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	1.0	1.1	0.8	1.0

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Experiencing a Serious Bacterial Infection
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ciprofloxacin or Ofloxacin	TMP-SMX	No Prophylaxis
Arm/Group Description	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.	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..	The patient will receive no prophylactic antibiotics.
Measure Participants	64	74	63
Number (95% Confidence Interval) [percentage of participants]	12.5 18.1%	6.8 8.9%	15.9 23.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciprofloxacin or Ofloxacin, TMP-SMX, No Prophylaxis
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments
	Method	Fisher Exact
	Comments	Target accrual=70 patients per arm to provide 92% power to detect a difference of 0.31 vs. 0.08 in the proportion of patients with serious infection.

Adverse Events

Time Frame	Three months.
Arm/Group Title	Ciprofloxacin or Ofloxacin		TMP-SMX		Observation
Arm/Group Description	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.		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..		No Prophylaxis: The patient will receive no prophylactic antibiotics.
All Cause Mortality
	Ciprofloxacin or Ofloxacin		TMP-SMX		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ciprofloxacin or Ofloxacin		TMP-SMX		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/69 (1.4%)		2/76 (2.6%)		0/67 (0%)
General disorders
Death	1/69 (1.4%)		0/76 (0%)		0/67 (0%)
Infections and infestations
Infection, thrush, allergic reaction	0/69 (0%)		1/76 (1.3%)		0/67 (0%)
Renal and urinary disorders
Renal failure	0/69 (0%)		1/76 (1.3%)		0/67 (0%)
Other (Not Including Serious) Adverse Events
	Ciprofloxacin or Ofloxacin		TMP-SMX		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/69 (1.4%)		1/76 (1.3%)		0/67 (0%)
Gastrointestinal disorders
GI bleed	1/69 (1.4%)		0/76 (0%)		0/67 (0%)
Infections and infestations
Thrush	0/69 (0%)		1/76 (1.3%)		0/67 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.