Clinical trial NCT00045292: Valacyclovir in Preventing Cytomegalovirus Infection in Patients Who Are Undergoing Donor Stem Cell Transplantation
Official title: A Phase III Multicenter Study of Cytomegalovirus Prophylaxis With Valacyclovir for the Prevention of Serious Fungal and Bacterial Infections Among Cytomegalovirus Seronegative Recipients of Cytomegalovirus Seropositive Sx Stem Cell Transplants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Keywords: infection
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
atypical chronic myeloid leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic neutrophilic leukemia
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
de novo myelodysplastic syndromes
myelodysplastic/myeloproliferative disease, unclassifiable
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
disseminated neuroblastoma
recurrent neuroblastoma
noncontiguous stage II adult diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
recurrent adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
recurrent adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
poor prognosis metastatic gestational trophoblastic tumor
previously treated childhood rhabdomyosarcoma
recurrent Wilms tumor and other childhood kidney tumors
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent childhood rhabdomyosarcoma
recurrent childhood large cell lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
refractory hairy cell leukemia
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antivirals such as valacyclovir act against viruses and may be effective in preventing cytomegalovirus. It is not yet known if valacyclovir is effective in preventing cytomegalovirus in patients undergoing stem cell transplantation.

PURPOSE: Randomized phase III trial to determine the effectiveness of valacyclovir in preventing cytomegalovirus in patients who are undergoing donor stem cell transplantation.

Detailed description: OBJECTIVES:

* Compare the occurrence of serious invasive fungal or bacterial infections during the first 270 days after transplantation in cytomegalovirus (CMV)-negative patients receiving a CMV-positive allogeneic stem cell transplantation and valacyclovir or placebo.
* Compare the occurrence of primary CMV infection within the first 100 days after transplantation in patients treated with these regimens.
* Compare the survival of these patients at 100 days and 270 days post-transplantation.
* Compare the occurrence of CMV disease at day 100 and day 270 post-transplantation in patients treated with these regimens.
* Compare the safety of these regimens in these patients.
* Correlate the presence of CMV in stem cell product with post-transplantation CMV infection in these patients.
* Determine if subclinical CMV infection results in a virus-specific immune response (humoral and cellular) in these patients.
* Compare the quality of life of patients treated with these regimens.
* Compare resource utilization (e.g., rates of hospitalization, number of days alive out of the hospital, days in the intensive care unit, days on mechanical ventilation, use of antimicrobials and filgrastim \[G-CSF\], and number of invasive procedures) in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and type of transplantation (matched related vs mismatched/unrelated). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral valacyclovir 4 times daily beginning with transplantation conditioning (usually day -5) and continuing until day 100 after transplantation. Patients receive high-dose acyclovir, instead of valacyclovir, IV every 8 hours beginning on day -1 and continuing until oral medications are tolerated. Allogeneic stem cells are infused on day 0.
* Arm II: Patients receive oral or IV placebo on the same schedule as in arm I. Quality of life is assessed at baseline and on days 50 and 100.

Patients are followed every 2 weeks for 6 months.

PROJECTED ACCRUAL: A total of 115-230 patients (58-115 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Disease requiring one of the following types of stem cell transplantation:

  * First myeloablative allogeneic peripheral blood stem cell
  * Unrelated cord blood
  * Bone marrow

    * Related or unrelated donor
    * T-cell depleted or non-T-cell depleted
    * CD34 selected or non-selected
* Patient must be cytomegalovirus (CMV)-seronegative and donor must be CMV-seropositive
* No transplantation with nonmyeloablative regimens, including any of the following:

  * Fludarabine and total body irradiation (TBI) (2 Gy or less)
  * TBI alone (2 Gy)
  * Fludarabine, cytarabine, and idarubicin
  * Fludarabine and melphalan (140 mg/m\^2 or less)
* No definite or probable pre-transplantation diagnosis of invasive mold infection (aspergillosis, fusariosis, or zygomycosis), including pulmonary or hepatic nodules consistent with invasive mold infection for which patients are receiving targeted prophylaxis with amphotericin or other mold-active products
* No pre-transplantation-CMV disease (gastrointestinal or pneumonia)

PATIENT CHARACTERISTICS:

Age

* 12 and over

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* HIV negative
* No hypersensitivity to acyclovir or valacyclovir
* Not pregnant
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics

Surgery

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Garrett Nichols, MD, MSC
role: STUDY_CHAIR
References: