Cmx001 as Therapy for Severe Adenovirus Infections in Immunocompromised Pediatric Patients: Single Experience in 5 Patients

Grimley, Michael; Marsh, Rebecca; Bleesing, Jack J.; Mehta, Parinda A.; Jodele, Sonata; Myers, Kasiani; Kumar, Ashish; Jordan, Michael B.; Edwards, Stephanie; Kennedy, Rebekah; Wilhelm, Jamie; Painter, Wendy; Anderson, M.; Filipovich, Alexandra H.; Davies, Stella M.

doi:10.1016/j.bbmt.2011.12.286

Cited by 3 publications

(2 citation statements)

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“…Cidofovir has been used in established ADV disease, yet its efficacy is not well documented. CMX001, a novel, orally administered, broad spectrum antiviral active against ADV, has shown promising results in case reports (10, 14, 15). A clinical trial of preemptive treatment of ADV viremia with CMX001 for prevention of ADV disease in HSCT is ongoing.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Lee

Chung

Xiao

et al. 2013

Biology of Blood and Marrow Transplantation

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Background ADV (adenovirus) is an important cause of viral mortality in hematopoietic stem cell transplantation (HSCT). T-cell depleted (TCD) HSCT are at increased risk of viral infections. We compared the rates and outcomes of ADV viremia and disease between TCD and conventional (CONV) HSCT at our institution. Methods This was an observational study of 624 adult and pediatric recipients of myeloablative HSCT at Memorial Sloan-Kettering Cancer Center from January 1, 2006, through March 11, 2011. Viral cultures and ADV polymerase chain reaction (PCR) were ordered as clinically indicated. ADV viremia by a quantitative PCR assay was defined as ≥1 positive value ≥1,000 copies/mL or ≥2 consecutive values at any value. Competing risk regression analyses were used to identify predictors for ADV viremia. Results Eight percent TCD and 4.0% CONV were noted to have ADV viremia at 1 year after HSCT (P=.041). Among TCD, 15% of children compared with 5% of adults developed ADV viremia (P=.008). Young age (Hazard Ratio [HR] 3.0; P<.001) and acute graft-versus-host-disease (GVHD) (HR 3.2; P=.001) were risk factors for ADV viremia. ADV viremia was a predictor of mortality (HR 6.0; P<.001). ADV disease developed in 3.5% TCD and 0.4% CONV HSCT (P=.022) with attributable mortality of 27%. Among TCD, grade 2–4 GVHD was a risk factor for ADV disease (HR 13; P<.001); age was not significant. More than 90% ADV disease cases had a viral load of ≥ 10,000 copies/mL. Conclusions Rates of ADV disease were 10-fold higher in TCD compared with CONV HSCT, predominantly in patients who developed acute GVHD. The benefit of preemptive therapy for ADV viral load ≥ 10,000 copies/mL for prevention of ADV disease in recipients of TCD grafts should be evaluated in prospective clinical trials.

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Section: Introductionmentioning

confidence: 99%

Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Lee

Chung

Xiao

et al. 2013

Biology of Blood and Marrow Transplantation

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“…Cidofovir has been used in established ADV disease and ADV viremia, yet its efficacy is based on small noncontrolled studies and case series [272][273][274]. Brincidofovir, a novel, orally administered, broadspectrum antiviral active against ADV, has shown promising results in case reports [277,281,282]. A small randomized placebo-controlled clinical trial of preemptive treatment of ADV viremia with brincidofovir confirmed the antiviral activity in HCT patients however [283].…”

Section: Adenovirus (Adv)mentioning

confidence: 99%

Impacts and Challenges of Advanced Diagnostic Assays for Transplant Infectious Diseases

Babady

Lee

Papanicolaou

et al. 2019

Principles and Practice of Transplant Infectious Diseases

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A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation

Marty

Winston

Chemaly

et al. 2019

Biology of Blood and Marrow Transplantation

175

122

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Cytomegalovirus (CMV) infection is a common complication of allogeneic hematopoietic cell transplantation (HCT). In this trial, we randomized adult CMV-seropositive HCT recipients without CMV viremia at screening 2:1 to receive brincidofovir or placebo until week 14 post-HCT. Randomization was stratified by center and risk of CMV infection. Patients were assessed weekly through week 15 and every third week thereafter through week 24 post-HCT. Patients who developed clinically significant CMV infection (CS-CMVi; CMV viremia requiring preemptive therapy or CMV disease) discontinued the study drug and began anti-CMV treatment. The primary endpoint was the proportion of patients with CS-CMVi through week 24 post-HCT; patients who discontinued the trial or with missing data were imputed as primary endpoint events. Between August 2013 and June 2015, 452 patients were randomized at a median of 15 days after HCT and received study drug. The proportion of patients who developed CS-CMVi or were imputed as having a primary endpoint event through week 24 was similar between brincidofovir-treated patients and placebo recipients (155 of 303 [51.2%] versus 78 of 149 [52.3%]; odds ratio, .95 [95% confidence interval, .64 to 1.41]; P = .805); fewer brincidofovir recipients developed CMV viremia through week 14 compared with placebo recipients (41.6%; P < .001). Serious adverse events were more frequent among brincidofovir recipients (57.1% versus 37.6%), driven by acute graft-versus-host disease (32.3% versus 6.0%) and diarrhea (6.9% versus 2.7%). Week 24 all-cause mortality was 15.5% among brincidofovir recipients and 10.1% among placebo recipients. Brincidofovir did not reduce CS-CMVi by week 24 post-HCT and was associated with gastrointestinal toxicity.

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Cmx001 as Therapy for Severe Adenovirus Infections in Immunocompromised Pediatric Patients: Single Experience in 5 Patients

Cited by 3 publications

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Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Impacts and Challenges of Advanced Diagnostic Assays for Transplant Infectious Diseases

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation

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