25 Levels of each biomarker in evaluable subjects were compared at baseline and at 6 months by using 2-tailed Mann-Whitney U tests and Wilcoxon matched-pairs signed-rank analyses. 24 For each event, cumulative incidence (CI) was analyzed with 2 other events as the competing risk events. Failure-free survival was estimated according to the Kaplan-Meier method, with treatment change, NRM, and malignancy relapse as the events. Differences between dose groups in subject baseline covariates were assessed by using the Mann-Whitney U test for continuous measures and Fisher’s exact test and the Fisher-Freeman-Halton test for categorical features. As an early stopping rule for futility, if after 7 subjects were enrolled on either cohort none had responded, enrollment to that cohort would then stop. Three or more responses in 16 evaluable subjects would be sufficient to exclude a 5% response rate and show consistency with 30% or better response rates. With 16 subjects in each cohort, an exact binomial test would have 90% power to detect a difference between a 5% response rate and a 30% response rate using a 0.10 one-sided significance level and an exact binomial test. Subjects with only acute GVHD, neutrophils 3 mg/L, transaminase >3 times the upper limit of normal (liver cGVHD per se was not an exclusion criterion), left ventricular ejection fraction <45%, active HIV-1, hepatitis B or C infection, and NIH lung score 3 were excluded. Additional inclusion criteria were Karnofsky performance score ≥60% and agreement to adhere to methods of contraception and other fertility control measures per Celgene Risk Evaluation and Mitigation Strategy (REMS) program. Extracorporeal photopheresis had to be stopped ≥4 weeks before study entry. Subjects had to be on a stable or decreasing dose of corticosteroids and/or any other concurrent systemic immunosuppression in the 4 weeks before study entry. Subjects had to be in complete remission of their cancer and have cGVHD deemed unresponsive or progressive on high-dose corticosteroids based on an extensive review of patient history and medical records at the time of study entry (progression in at least one organ 19 while on an average dose of ≥0.5 mg/kg per day of prednisone for ≥8 weeks and/or subsequent systemic therapies). 18 Subjects were enrolled in a National Cancer Institute Institutional Review Board–approved treatment protocol (#NCT01688466, conducted in accordance with the Declaration of Helsinki), treated, and followed up as outpatients at the NIH Clinical Center. Subjects were 18 to 75 years of age with moderate to severe cGVHD (classic and overlap) per National Institutes of Health (NIH) criteria. Pomalidomide 0.5 mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. There was 1 death in the low-dose cohort from bacterial pneumonia.
Eight subjects in the high-dose cohort had dose decreases because of adverse events. The most frequent adverse events were lymphopenia, infection, and fatigue.
Extend flowjo trial skin#
Median change from the baseline in body surface area involvement of skin cGVHD was −7.5% (–10% to 35% P =. Nine had improvement in National Institutes of Health joint/fascia scores ( P =. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. All were partial responses, with no difference in ORR between the cohorts. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17 low-dose cohort) or 2 mg per day at a starting dose of 0.5 mg per day increasing to 2 mg per day over 6 weeks (n = 17 high-dose cohort).
Extend flowjo trial trial#
We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Sclerotic skin manifestations are especially difficult to treat. Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge.