Moxifloxacin in Preventing Bacterial Infections in Patients Who Have Undergone Donor Stem Cell Transplant

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT00324324

Collaborator

National Cancer Institute (NCI) (NIH)

240

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: A donor stem cell transplant can lower the body's immune system, making it difficult to fight off infection. Giving antibiotics, such as moxifloxacin, may help prevent bacterial infections in patients who have recently undergone donor stem cell transplant. It is not yet known whether moxifloxacin is more effective than a placebo in preventing bacterial infections in patients who have recently undergone donor stem cell transplant.

PURPOSE: This randomized phase III trial is studying moxifloxacin to see how well it works compared with a placebo in preventing bacterial infections in patients who have recently undergone donor stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Chronic Myeloproliferative Disorders Gestational Trophoblastic Tumor Infection Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Neuroblastoma Ovarian Cancer Testicular Germ Cell Tumor	Drug: moxifloxacin hydrochloride Drug: Placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

Assess the safety and tolerability of giving prophylactic moxifloxacin hydrochloride during the post-engraftment phase in patients who have undergone allogeneic stem cell transplantation. (Pilot study)
Compare the efficacy, in terms of reducing the incidence of clinically and microbiologically documented bacterial infections, in patients who have undergone allogeneic stem cell transplantation treated with prophylactic moxifloxacin hydrochloride vs placebo during the post-engraftment phase. (Phase III)

Secondary

Determine the incidence of clinically and microbiologically documented bacterial infections in these patients. (Pilot study)
Assess the impact of moxifloxacin hydrochloride on the incidence of bacteremia in these patients. (Phase III)
Compare the percentage of time on systemic antibiotics and days hospitalized in patients treated with these regimens. (Phase III)
Compare the incidence of veno-occlusive disease of the liver in patients treated with these regimens. (Phase III)
Compare the incidence and severity of graft-versus-host disease in patients treated with these regimens. (Phase III)
Compare the infection-related mortality and overall mortality of patients treated with these regimens.

OUTLINE: This is a pilot study followed by a randomized, double-blind, placebo-controlled, multicenter phase III study. Patients are stratified according to gender and race (white vs. non-white). The first 20 patients are assigned to the pilot study.

Patients assigned to the pilot study receive oral moxifloxacin hydrochloride once daily beginning after neutrophil recovery (ANC > 1,500/mm³) from allogeneic stem cell transplantation (ASCT) and continuing until day 100 post-transplantation in the absence of disease progression or unacceptable toxicity. Subsequent patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral moxifloxacin hydrochloride once daily beginning after neutrophil recovery (ANC > 1,500/mm³) from ASCT and continuing until day 100 post-transplantation.
Arm II: Patients receive oral placebo once daily beginning after neutrophil recovery (ANC > 1,500/mm³) from ASCT and continuing until day 100 post-transplantation.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at day 120 post-transplantation.

PROJECTED ACCRUAL: A total of 240 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Randomized, Double Blinded, Placebo-Controlled Trial of Antibacterial Prophylaxis for the Prevention of Bacterial Infections in the Post-Engraftment Phase After Allogeneic Hematopoeitic Stem Cell Transplantation

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Apr 1, 2007

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: moxifloxacin hydrochloride Moxifloxacin 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue	Drug: moxifloxacin hydrochloride Moxifloxacin/Placebo 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue
Placebo Comparator: Sugar pill Placebo 1 capsule orally once a day through D+100 after bone marrow transplant, then discontinue	Drug: Placebo Moxifloxacin/Placebo 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue

Arm

Intervention/Treatment

Active Comparator: moxifloxacin hydrochloride

Moxifloxacin 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue

Drug: moxifloxacin hydrochloride

Moxifloxacin/Placebo 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue

Placebo Comparator: Sugar pill

Placebo 1 capsule orally once a day through D+100 after bone marrow transplant, then discontinue

Drug: Placebo

Moxifloxacin/Placebo 400 mg capsule orally once a day through D+100 after bone marrow transplant, then discontinue

Outcome Measures

Primary Outcome Measures

Safety and tolerability [1 to 120 days post bone marrow transplant]

Secondary Outcome Measures

Incidence of bacteremia [1 to 120 days post bone marrow transplant]
Incidence and severity of graft-versus-host disease [1 to 120 days post bone marrow transplant]
Infection-related mortality [1 to 120 days post bone marrow transplant]
Overall mortality [1 to 120 days post bone marrow transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Must be planning to undergo or have completed allogeneic stem cell transplantation (ASCT)
Must not be undergoing a nonmyeloablative ASCT
Must not require antibiotic prophylaxis against bacterial pathogens during the post-engraftment phase as per ASCT protocol
No known colonization with an antimicrobial-resistant organism normally sensitive to quinolones that is known to increase infection incidence (i.e., ciprofloxacin-resistant Pseudomonas not allowed; vancomycin-resistant Enterococcus and methicillin-resistant Staphylococcus aureus allowed)

PATIENT CHARACTERISTICS:

Life expectancy ≥ 100 days
Not pregnant or nursing
Fertile patients must use effective contraception
Negative pregnancy test
No known hypersensitivity to fluoroquinolones
No prolonged QTc interval on EKG (i.e., QTc > 440 milliseconds)
No uncontrolled hypokalemia

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No concurrent class IA (e.g., quinidine or procainamide) or class III (e.g., amiodarone or sotalol) antiarrhythmics
No concurrent intravenous antibiotics for pre-enrollment infections except vancomycin, linezolid, dalfopristin, or quinupristin (Synercid®)