Clinical trial NCT00324324: Moxifloxacin in Preventing Bacterial Infections in Patients Who Have Undergone Donor Stem Cell Transplant
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: 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
Keywords: infection
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
atypical chronic myeloid leukemia, BCR-ABL negative
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
myelodysplastic/myeloproliferative neoplasm, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
poor prognosis metastatic gestational trophoblastic tumor
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent neuroblastoma
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
recurrent small lymphocytic lymphoma
recurrent malignant testicular germ cell tumor
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
refractory multiple myeloma
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
splenic marginal zone lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage II ovarian epithelial cancer
stage III adult Burkitt lymphoma
stage III adult Hodgkin lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III multiple myeloma
stage III ovarian epithelial cancer
stage III small lymphocytic lymphoma
stage III malignant testicular germ cell tumor
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV adult Burkitt lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV breast cancer
stage IV chronic lymphocytic leukemia
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV ovarian epithelial cancer
stage IV small lymphocytic lymphoma
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-05-11
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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®)

Primary outcomes:
measure: Safety and tolerability
timeFrame: 1 to 120 days post bone marrow transplant
Secondary outcomes:
measure: Incidence of bacteremia
timeFrame: 1 to 120 days post bone marrow transplant
measure: Incidence and severity of graft-versus-host disease
timeFrame: 1 to 120 days post bone marrow transplant
measure: Infection-related mortality
timeFrame: 1 to 120 days post bone marrow transplant
measure: Overall mortality
timeFrame: 1 to 120 days post bone marrow transplant
Other outcomes:
Locations:
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Joseph Bubalo, PharmD, BCPS, BCOP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bubalo JS, Leis JF, Curtin PT, et al.: A randomized, double-blinded, pilot trial of aprepitant added to standard antiemetics during conditioning therapy for hematopoietic stem cell transplant (HSCT). [Abstract] J Clin Oncol 25 (Suppl 18): A-9112, 520s, 2007.