Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies. EXPERIMENTAL DESIGN: A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4, 7, or 10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression. RESULTS: All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns. CONCLUSION: Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

Patient experience with follitropin alfa prefilled pen versus previously used injectable gonadotropins for ovulation induction in oligoanovulatory women.

OBJECTIVE: To evaluate patient satisfaction with the follitropin alfa prefilled pen (Gonal-f RFF Pen), compared with previously used injectable gonadotropins (vial/ampoules and syringe), in women undergoing ovulation induction (OI). RESEARCH DESIGN AND METHODS: Women aged 18-40 years undergoing OI for oligoanovulatory infertility were enrolled from nine US fertility centers in this prospective, open-label clinical trial. Participants received recombinant follitropin alfa using a prefilled pen. Patient satisfaction was determined using a pre-treatment questionnaire to assess gonadotropin treatments undertaken within 6 months of study initiation and an in-treatment questionnaire to assess satisfaction with the prefilled pen. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who preferred the prefilled pen compared to previous injectable gonadotropin therapies. Efficacy and safety were also assessed. RESULTS: Seventy-three subjects were screened for the study; 62 enrolled, were treated with the follitropin alfa pre-filled pen, and 61 completed the in-treatment questionnaire. Sixty-one of 61 patients who stated a preference preferred the prefilled pen to previous injectable gonadotropin therapies (61/61; 100%; 95% confidence interval: [94.1-100.0%]). One patient did not state a preference. Of these 61 patients, 54 (89%) found that the prefilled pen instructions were easy to understand compared to 17 of 59 (29%) who thought instructions for the conventional syringes were easy to understand. When preparing their dose, significantly fewer patients contacted their healthcare provider two or more times during the treatment cycle when receiving treatment with the prefilled pen (2/61, 3%) than during the first treatment cycle with prior gonadotropin treatment, 11/59 (19%, p = 0.007). The pen interfered slightly or not at all with patients' normal daily activities in 61 of 61 patients (100%) versus 50 of 59 patients (85%) who had this opinion regarding injections during their prior treatment cycles (p = 0.003). All 61 patients who stated a method of injection preference found the prefilled pen less stressful to use than syringes and would recommend the pen to another woman considering gonadotropin treatment. A total of 10/62 (16%) subjects reported 18 treatment-emergent adverse events (AEs). Two cases of ovarian hyperstimulation syndrome occurred post-treatment and one serious AE occurred (post-treatment ectopic pregnancy). Injection site reactions were generally mild to moderate, with mild itching (6 patients, 9.7%) and moderate redness in one patient. Fifteen patients reported mild redness (24.2%). Mild bruising (21.0%), mild pain (33.9%), and mild burning (32.3%) were also reported by patients. Seven patients (11.3%) had moderate pain. CONCLUSIONS: In this open-label, non-comparative study, patients undergoing OI preferred administering gonadotropins using the follitropin alfa prefilled pen compared to their prior use of vials/ampoules and a syringe. Patients using the prefilled pen found it less stressful, easier to use and more convenient than a conventional syringe and would recommend the pen to another woman considering gonadotropin treatment.

Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologies.

OBJECTIVE: To compare the safety and efficacy of single-dose cetrorelix acetate (3 mg) and daily ganirelix acetate (0.25 mg) in the inhibition of premature LH surge in women undergoing cycle-programmed ovarian stimulation before Assisted Reproductive Technology (ART). DESIGN: Prospective, open-label, randomized, comparative study. SETTING: Sixteen ART centers in the United States. PATIENT(S): One hundred eighty-five infertile patients undergoing ART. INTERVENTION(S): Single injection of cetrorelix (3 mg SC) or daily dose of ganirelix (0.25 mg SC) was administered when the lead follicle was > or =14 mm. Daily cetrorelix (0.25 mg) was administered if the criteria for hCG administration were not met 4 days after receiving 3 mg of cetrorelix. MAIN OUTCOME MEASURE(S): Percentage of patients who did not have a premature LH surge, defined as LH <10 IU/L on the day of hCG administration. The IVF and embryo transfer (ET) outcomes were assessed. RESULT(S): No patient in either treatment group had a premature LH surge. There were no statistically significant differences between treatments for any IVF/intracytoplasmic sperm injection (ICSI) or ET outcomes, including pregnancy rate (PR). However, cetrorelix required significantly fewer injections than ganirelix. Similar safety profiles were observed. CONCLUSION(S): Cetrorelix and ganirelix effectively prevented LH surges in oral contraceptive (OC) pill-programmed, flexible protocols, with similar safety profiles and PRs; however, cetrorelix required significantly fewer injections, increasing patient convenience.