Long-Term Survival Is Comparable between Palifermin-Treated and Placebo-Treated Patients (Pts) with Hematologic Malignancies (HM) Undergoing High-Dose Chemotherapy and Total Body Irradiation Followed by Autologous Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2925-2925 ◽  
Author(s):  
Ricardo Spielberger ◽  
Christos Emmanouilides ◽  
William Bensinger ◽  
Alan Rong ◽  
Alessandra Cesano ◽  
...  
Keyword(s):  
Controlled Study ◽  
Secondary Malignancies ◽  
Double Blind ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Double Blind Placebo ◽  
Disease Outcomes ◽  
Long Term Follow Up

Abstract Oral mucositis (OM) is a severely debilitating side effect of chemoradiotherapy that often causes significant pain, diminished quality of life, and increased risk of infections. Palifermin decreases the incidence and duration of severe OM in HM pts receiving myelotoxic therapy and HSCT. Palifermin safety and efficacy have not been established in the non-HM setting. Since the rHuKGF receptor is not expressed by HM, palifermin is not expected to interfere with long-term disease outcomes in this pt population. Aim: We assessed palifermin’s effects on the long-term disease outcomes (survival, disease progression, secondary malignancies) in pts with HM. Methods: Long-term follow-up data were pooled from a 1998 phase 2, double-blind, placebo-controlled study (n=86) and a 2000 double-blind, placebo-controlled phase 3 study (n=212). The analysis included 152 pts treated with palifermin and 146 pts treated with placebo. Pts were assessed at 6-month intervals during the first year and annually thereafter until death or loss to follow-up. The Kaplan-Meier (K–M) method provided estimates of the safety endpoints. Data reported here are as of August 2004. Results: There were 298 pts (152 palifermin: 146 placebo) monitored for long-term follow-up. The median follow-up period was 23.3 months for palifermin and 23.5 months for placebo. The overall survival and progression-free survival curves (p=0.474 and p=0.253, respectively) are similar between the palifermin and placebo groups. Secondary malignancies occurred in only 6 of 152 (3%) palifermin and 5 of 146 (4%) placebo pts. All secondary malignancies were myelodysplastic syndromes: 9 patients with diagnoses of Non-Hodgkin’s lymphoma and 2 patients of Hodgkin’s Disease. The number of deaths was similar between the groups (30% palifermin; 27% placebo); most deaths occurred within 12 months of randomization and were attributable to the underlying HM disease. Conclusion: Use of palifermin for the prevention of severe OM has shown no negative impact on long-term disease outcomes, including survival, in the HSCT setting for patients with HM.

scholarly journals P.006 Efficacy of adjunctive brivaracetam in adult patients with secondarily generalized tonic-clonic seizures at baseline: pooled results from long-term follow-up trials

2019 ◽  
Vol 46 (s1) ◽  
pp. S15
Author(s):  
BD Moseley ◽  
A Diaz ◽  
S Elmoufti ◽  
J Whitesides
Keyword(s):  
Controlled Trials ◽  
Open Label ◽  
Efficacy Data ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Long Term Follow Up ◽  
Clonic Seizures ◽  
Post Hoc

Background: Previous post-hoc analysis of three 12-week, double-blind, placebo-controlled trials showed adjunctive brivaracetam (BRV) reduced focal and secondarily generalized tonic-clonic seizures (SGTCS; Type IC) in patients with baseline SGTCS. This analysis explored long-term efficacy of adjunctive BRV in these patients. Methods: Patients (≥16 years) with focal seizures with SGTCS at Baseline were identified from 12-week double-blind, placebo-controlled trials (NCT00490035/NCT00464269/NCT01261325) and subsequent open-label, long-term follow-up (LTFU) trials (NCT00175916/NCT00150800/NCT01339559). Outcomes were assessed at protocol-specified time-points (up to 60 months). We report post-hoc efficacy data for patients receiving BRV (50–200 mg/day). Results: At double-blind Baseline, 409 patients had SGTCS (mean epilepsy duration: 22.2 years); 28.4%, 38.9%, and 32.8% had 0–1, 2–4, and ≥5 previous AEDs. Baseline median seizure frequency/28 days was 8.1 (focal) and 3.0 (SGTCS only). 325/409 patients (79.5%) entered LTFU. In the 12-month (n=150), 24-month (n=89), 36-month (n=73), 48-month (n=68) and 60-month (n=57) exposure cohorts, median percent reduction from Baseline in SGTCS frequency/28 days was 81.1%, 84.0%, 89.2%, 91.0%, and 90.6%, respectively. ≥50% responder rates for SGTCS were 75.3%, 78.7%, 80.8%, 79.4%, and 78.9%. No safety concerns were identified. Conclusions: Adjunctive BRV (50–200 mg/day) reduced SGTCS frequency during LTFU (up to 60 months) in patients with SGTCS at Baseline.

scholarly journals Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma

2001 ◽  
Vol 113 (4) ◽  
pp. 1035-1043 ◽  
Author(s):  
Eugene V. McCloskey ◽  
Janet A. Dunn ◽  
John A. Kanis ◽  
Ian C. M. MacLennan ◽  
Mark T. Drayson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Randomized Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Long Term Follow Up

No Difference in Survival or Long-Term Disease Outcomes in Palifermin-Treated Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1664-1664
Author(s):  
Ricardo Spielberger ◽  
Mary Territo ◽  
Simon Durrant ◽  
Stephen Nimer ◽  
John McCarty ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hematological Malignancies ◽  
Safety Data ◽  
Hematologic Malignancies ◽  
Secondary Malignancies ◽  
Hematopoietic Stem ◽  
Follow Up Study ◽  
Disease Outcomes

Abstract Background: Oral mucositis is an adverse effect of myeloablative therapy which has serious clinical and economic consequences as well as a negative impact upon quality of life. The duration and severity of oral mucositis can be reduced by administering palifermin to patients with hematological malignancies receiving myeloablative therapy and undergoing hematopoietic stem cell transplantation (HSCT). However, we still require additional data on the long-term disease outcomes of patients treated with palifermin. Therefore we present here the long-term, safety data for palifermin-treated HSCT patients followed up for approximately 60 months after the last palifermin dose. Methods: The long-term safety data were collected during the follow-up phase of 4 parent trials where patients had received at least one dose of palifermin or placebo. Study assessments included overall survival (OS), progression-free survival (PFS), and secondary malignancies. Assessments were made at 6-month intervals during year 1 and annually thereafter until death or loss to follow-up. Kaplan-Meier curves for overall survival and PFS were calculated and the treatment groups were compared using stratified log-rank test. Results: Altogether 662 patients were randomized to treatment and received either palifermin or placebo (421 palifermin, 241 placebo); 538 patients entered the follow-up study (342 palifermin, 196 placebo). The median follow-up time for patients alive at last visit was 49.8 months (palifermin N=290) and 49.5 months (placebo N=169). There were 131 (32%) and 72 (30%) deaths in the palifermin and placebo groups, respectively. The overall survival curves were similar for both groups (p=0.717). Disease progression occurred in 167 (41%) palifermin- and 87 (36%) placebo-treated patients; the difference in PFS between the two groups was non-significant (p=0.280). Secondary malignancies were observed in 8% of patients in both groups: the incidence of secondary hematologic malignancies was 4% (palifermin: 14/342) versus 5% (placebo: 10/196) while the incidence of solid tumors was 2% in both groups. Conclusion: The results of this 60-month follow-up study indicate that long-term disease outcomes are not affected by administering palifermin to patients with hematological malignancies who are receiving myeloablative therapy and undergoing HS. There was no difference in OS and PFS between the palifermin and placebo groups. Furthermore there was no difference in the incidence of secondary malignancies between the two patient groups. The incidence of secondary hematologic malignancies and solid tumors was low, comparable between groups, and within the expected range for this patient population.

scholarly journals SAT-163 Status at 10 Years: Long-Term Follow-Up for a Phase 2a Study of High-Specific-Activity (HSA) I 131 Iobenguane in Patients (Pts) with Relapsed/Refractory High-Risk Neuroblastoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Judith G Villablanca ◽  
John M Maris ◽  
Nancy Stambler ◽  
Duo Zhou ◽  
Vincent A DiPippo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Whole Body ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Mixed Response ◽  
Nonhematologic Toxicity ◽  
Long Term Follow Up

Abstract Background: Metaiodobenzylguanidine (MIBG; iobenguane), a guanethidine derivative, is a substrate for norepinephrine reuptake transporter which is highly expressed on the surface of neuroblastoma cells. AZEDRA® (HSA I-131 MIBG) has been approved by the FDA for the treatment of pheochromocytoma and paraganglioma, in pts 12 years and older with MIBG avid, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. The aim of this study was to establish the maximum tolerated dose in children with neuroblastoma, with secondary aims of assessing overall response and tumor and organ dosimetry. Here we report current long-term survival and toxicity data. Methods: Eligible pts were 1-30 years old with resistant neuroblastoma. A diagnostic dose of HSA I-131 MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. To prevent prolonged myelosuppression, autologous hematopoietic stem cells were infused 14 days after therapy. Response and toxicity were evaluated on day 60. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/µL within 28 days, or platelets to greater than 20,000/µL within 56 days, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: First pt was enrolled in June 2008. 15 pts total were evaluable at 12 (n=5), 15 (n=3), and 18 (n=7) mCi/kg. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight pts had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. MYC-N amplification was present in two of 11 pts with available results. Of the 15 treated pts, 1 had a complete response, 3 had a partial response, 1 had a mixed response and 6 had stable disease. The remaining 4 had progressive disease. Twelve of the 15 evaluable pts received non-protocol therapy after HSA I-131 MIBG, the remaining 3 died due to tumor without further therapy. At 3.6 years of follow-up the overall survival was 26.7% (95% CI, 8.3%-49.6%). As of March 2018, one remaining pt is in long term follow up with an overall survival of 8.4 years. This pt was previously reported to have a secondary malignancy of myelodysplastic syndrome which has been in remission since receiving an allogenic bone marrow transplant in March 2014. Conclusions: HSA I-131 MIBG contributed to long term median survival of two years and was well tolerated. Treatment showed promising activity in the absence of significant nonhematologic toxicity.

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