valganciclovir to prevent cytomegalovirus infection in patients following donor stem cell transplantation

Conditions: Infection

Summary: rationale: antivirals such as valganciclovir act against viruses and may be effective in preventing cytomegalovirus. it is not yet known if valganciclovir is effective in preventing cytomegalovirus. purpose: this randomized phase iii trial is studying valganciclovir to see how well it works in preventing cytomegalovirus in patients who have undergone donor stem cell transplantation.

objectives: primary * compare cytomegalovirus (cmv) disease and non-cmv invasive infection-free survival in patients undergoing allogeneic hematopoietic stem cell transplantation treated with valganciclovir vs placebo. * compare the incidence of cmv disease in patients treated with these drugs. * compare the incidence of other severe invasive bacterial and fungal infections and overall survival in patients treated with these drugs. secondary * compare the incidence of cmv infection or disease at baseline and at days 270 and 640 after allogeneic hematopoietic stem cell transplantation in patients treated with these drugs. * compare the incidence of herpes simplex virus and varicella-zoster virus infections at baseline and day 270 in patients treated with these drugs. * determine the safety of valganciclovir in these patients. * compare the quality of life of patients treated with these drugs. * compare cmv-specific immune reconstitution in patients treated with these drugs. outline: this is a randomized, double-blind, placebo-controlled, multicenter study. patients are stratified according to participating center, prior neutropenia (yes vs no), and presence of refractory graft-versus-host disease requiring secondary therapy (yes vs no). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive oral valganciclovir daily. * arm ii: patients receive oral placebo daily. treatment begins around day 80-120 post-transplantation and continues until day 270 post-transplantation in the absence of active infection or unacceptable toxicity. patients developing active cytomegalovirus (cmv) infection receive induction doses of ganciclovir iv or open-label oral valganciclovir for 1 week followed by open-label oral valganciclovir maintenance dosing until cmv can no longer be detected. quality of life is assessed at baseline and days 180 and 270 post-transplantation. patients are followed at days 400, 520, and 640 post-transplantation. projected accrual: a total of 184 patients (92 per treatment arm) will be accrued for this study.

Eligibility criteria:
disease characteristics: * have undergone allogeneic peripheral blood stem cell, cord blood, or marrow transplantation (related or unrelated, t-cell depleted or non-t-cell depleted, cd34-selected or non-selected, or myeloablative or non-myeloablative) within the past 80-120 days * positive pre-transplantation cytomegalovirus (cmv) serology of recipient and/or donor * seropositive recipients with one of the following: * cmv infection before day 80, as determined by: * pp65 antigenemia * cmv dna in plasma * peripheral blood leukocytes (pbl) or whole blood at any level detected by polymerase chain reaction or hybrid capture * cmv pp67 mrna * cmv viremia by blood culture * surveillance bronchoalveolar lavage (culture or cytology) * cmv disease more than 6 weeks prior to enrollment * presence of graft-versus-host disease (gvhd) at enrollment * acute gvhd that requires treatment with systemic corticosteroids of doses greater than 0.5 mg/kg or * chronic clinically extensive gvhd requiring treatment with corticosteroids * continuous prophylaxis with ganciclovir, foscarnet, or cidofovir between engraftment and day 80 or * seronegative recipient with seropositive donor who has cmv infection before day 80 * no rising or uncontrolled cmv load (pp65 antigenemia levels no greater than 1/slide or no greater than 100 copies of cmv dna per ml of plasma or per million pbl allowed) * no cmv disease within 6 weeks prior to randomization * no leukemic relapse * cytogenetic or molecular relapse allowed patient characteristics: age: * 16 and over performance status: * not specified life expectancy: * at least 2 weeks hematopoietic: * absolute neutrophil count at least 1,000/mm\^3 for at least 1 week prior to enrollment hepatic: * not specified renal: * creatinine no greater than 2.5 mg/ml other: * no hypersensitivity to ganciclovir or valganciclovir * no uncontrolled diarrhea or severe gastrointestinal disease that would preclude oral medication * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 90 days after study participation * hiv negative * proficient in english prior concurrent therapy: biologic therapy: * see disease characteristics chemotherapy: * not specified endocrine therapy: * see disease characteristics radiotherapy: * not specified surgery: * not specified other: * prior ganciclovir, foscarnet, cidofovir, high-dose acyclovir, or valacyclovir as prophylaxis or preemptive therapy allowed * no concurrent prophylactic foscarnet, cidofovir, or ganciclovir (iv or oral) * no concurrent prophylactic high-dose acyclovir (more than 800 mg twice daily), valacyclovir (more than 500 mg twice daily), cidofovir (more than 0.5 mg/kg per week), or famciclovir (more than 500 mg/day) except for limited treatment courses at higher doses for varicella-zoster virus infections * concurrent low-dose (≤ 0.5 mg/kg per week) cidofovir allowed for limited treatment courses

Keywords: infection