Prolonged E. Coli Asparaginase Therapy Does Not Improve Significantly the Outcome for Children with Low and Average Risk Acute Lymphoblastic Leukemia (ALL) and Non Hodgkin Lymphoma (NHL): Final Report of the EORTC-CLG Randomized Phase III Trial 58951

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 134-134
Author(s):  
Veerle Mondelaers ◽  
Stefan Suciu ◽  
Barbara De Moerloose ◽  
Alina Ferster ◽  
Françoise Mazingue ◽  
...  
Keyword(s):  
Risk Group ◽  
Phase Iii ◽  
Final Report ◽  
Average Risk ◽  
European Organization ◽  
Childhood All ◽  
Similar Treatment ◽  
Phase Iii Trial ◽  
To Receive

Abstract Abstract 134 Background: Asparaginase (ASP) is an essential component in combination chemotherapy for childhood ALL and NHL, as indicated by several randomized trials. However, the optimal number of ASP administrations is still unknown. We conducted a randomized phase III trial comparing conventional E.coli ASP regimen (short-ASP, 12 doses) with prolonged E.coli ASP therapy (long-ASP, 24 doses). Methods: The European Organization for Research and Treatment of Cancer Children's Leukemia Group (EORTC-CLG) phase III 58951 trial was open to de novo ALL or NHL patients (pts) < 18 y. This BFM-based study addressed 2 main randomized questions. The first evaluated the value of dexamethasone (DEX, 6mg/m2/d) vs prednisolone (PRED, 60mg/m2/d) in induction for all pts. In the second question all non-very high risk (VHR) pts were randomized for either short- or long-ASP. All patients had to receive 8×10000 U/m2 in induction. In the short-ASP arm pts had to receive 4×10000 U/m2 in late intensification; pts in the long-ASP arm had to receive 8×5000 U/m2E.coli ASP injections in consolidation and 8 (4×10000 U/m2 + 4×5000U/m2) in late intensification. Patients with grade ≥2 allergy to E.coli ASP had to be switched to equivalent doses of Erwinia or PEG ASP. Central randomization was stratified by the 1st randomized arm, risk group (VLR, AR1, AR2) and center. The primary endpoint of the study was disease-free survival (DFS), secondary endpoints were overall survival (OS) and toxicity. Intention-to-treat analysis was performed. Results: Between December 1998 and August 2008, 2038 patients were randomized for the 1st question and 1552 pts, ALL (n=1481) and NHL (n=71), were randomly assigned to receive long-ASP (n=775) or short-ASP (n=777). At a median follow-up of 7 years there were 97 vs 112 events in the long- vs short-ASP group (see table). The 8-year DFS rate was 87.0% in the long-ASP and 84.2% in short-ASP group (hazard ratio (HR) = 0.87, 95% CI 0.66–1.14, 2-sided logrank p=0.30). The 8-year OS rate was comparable in both treatment arms: 92.6% in the long-ASP group and 91.3% in the short-ASP group (HR = 0.89, 95% CI 0.61–1.29, 2-sided log rank p=0.53). Similar treatment differences were observed in each risk group, in randomized arm (PRED vs DEX), and B- and T-lineage ALL pts. The incidence of grade 3–4 infection was higher in the long- vs short-ASP group during consolidation (25.2% vs 14.5%) and late intensification (22.6% vs 15.9%). This difference was more pronounced in pts who were randomly assigned to DEX (see table). In the long- vs short-ASP group grade 2–4 allergy to ASP was 22.5% vs 0.3% in consolidation and 10.3% vs 21.5% in late intensification. During the whole treatment period, the incidence of grade 2–4 allergy was 30.5% in the long-ASP arm and 21.7% in the short-ASP arm. In the long- vs short-ASP arm approximately 67% vs 95% pts received at least the total number of E.coli or equivalent ASP administrations as planned according to the treatment arm. Conclusion: At long follow-up (median= 7 yrs) prolonged E.coli asparaginase therapy in consolidation and late intensification for VLR and AR pts did not improve significantly the outcome. Intensive ASP treatment did increase infection rate in consolidation and late intensification and resulted in more grade 2–4 allergic reactions. In the future, we aim to improve outcome rates by the use of PEG ASP and monitoring of asparaginase activity and antibody formation. Disclosures: No relevant conflicts of interest to declare.

Improved Outcome with Pulses of Vincristine and Steroids in Continuation Therapy of Children with Average Risk Acute Lymphoblastic Leukemia (ALL) and Non Hodgkin Lymphoma (NHL): Final Report of the EORTC Randomized Phase III Trial 58951

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 11-11 ◽  
Author(s):  
Barbara De Moerloose ◽  
Stefan Suciu ◽  
Yves Bertrand ◽  
Francoise Mazingue ◽  
Alain Robert ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Final Report ◽  
Average Risk ◽  
Childhood All ◽  
Non Hodgkin Lymphoma ◽  
Continuation Therapy ◽  
The Impact

Abstract Background: An overview of trials dating back to the ‘70s and ‘80s has shown that addition of vincristine (VCR)+prednisone/prednisolone pulses to continuation therapy of childhood ALL, i.e. 6-mercaptopurine (6-MP) + methotrexate (MTX), improved disease-free survival (DFS) (Lancet, 1996). However, a recent randomized intergroup trial (IGT) has shown that, when given to intermediate risk (age&lt;1 or &gt;=6 yrs or WBC&gt;20×109/L) patients (pts) treated according to the BFM protocol, VCR+dexamethasone (DEX) pulses in continuation therapy failed to improve DFS and overall survival (Lancet, 2007). Methods: In 12/1998, EORTC CLG started the randomized phase III 58951 trial addressing 3 questions: R1) the value of DEX vs PRED in induction; R2) the value of prolonged (24 injections) vs conventional (12 injections) duration of L-asparaginase (ASPA) courses during consolidation and late intensification; R3) for average risk (AR) pts only: the value of 6 (VCR+corticosteroid) pulses every 10 weeks during continuation therapy. The corticoid of the pulses was that assigned to the patient at R1: DEX (6 mg/sm/d) or prednisolone (PRED) (60 mg/sm/d) during 7 days. AR pts were defined by being neither low risk (hyperploidy &gt; 50 or DNI&gt;1.16, and WBC&lt;10×109/L and no extramedullary involvement) nor very high risk (Leukemia 2000). A total of 81 pts from the EORTC 58951 trial were included in the IGT study. Randomization was done centrally, and the main endpoint was DFS; secondary endpoints were OS and toxicity. Intent-to-treat analysis was used. Results: Between 6.1999 and 11.2004, 411 pts, ALL (N=384) and NHL (N=27), were randomized for the pulse question. In the Pulses group, 101 vs 101 pts were randomized for PRED vs DEX. At a median follow-up of 6.3 years, there were 19 vs 34 DFS events for the Pulses vs No Pulses comparison: BM (10 vs 16), CNS only (1 vs 4), other isolated (2 vs 3), BM+CNS (2 vs 5), BM+other (4 vs 4), death in CR (0 vs 2). The 6-year DFS rate from randomization was 90.6% (SE 2.1%) in the Pulses group and 82.8% (SE 2.8%) in the No Pulses group (hazard ratio (HR) = 0.54, 95% CI 0.32–0.94, 2-sided logrank p=0.027). The impact of pulses on DFS was similar in the PRED group (HR=0.56) and the DEX group (HR=0.59). In girls the treatment difference seemed to be more pronounced (HR=0.25, 99% CI 0.04–1.25; p=0.015) than in boys (HR=0.71, 99% CI 0.30–1.66; p=0.30), and also in those having been randomized to receive conventional duration of ASPA courses (HR=0.46, 99% CI 0.18–1.19; p=0.03) than in prolonged ASPA arm (HR=0.87, 99% CI 0.23–3.29; p=0.78). Grade 3–4 hepatic toxicity was lower in the Pulses group (30% vs 40%); incidence of grade 2–3 osteonecrosis was 4.4% (Pulses) vs 2% (No Pulses) and pancreatitis rate was 4.9% (Pulses) vs 2.9% (No Pulses). Conclusion: VCR+corticosteroid pulses, at long follow-up (median=6.3 yrs), significantly improved the DFS, particularly in pts having received conventional duration of ASPA. Pulses did not increase toxic effects. In future, for AR pts treated according to the BFM protocol, pulses should become a standard component of therapy.

Phase III Trial of Immunotherapy with Recombinant Interleukin-2 (rIL-2) Versus Observation in Patients < 60 Years with Acute Myeloid Leukemia (AML) in First Remission (CR1): Preliminary Results from Cancer and Leukemia Group B (CALGB) 19808.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 157-157 ◽  
Author(s):  
Jonathan E. Kolitz ◽  
Vera Hars ◽  
Daniel J. DeAngelo ◽  
Steven L. Allen ◽  
Thomas C. Shea ◽  
...  
Keyword(s):  
Survival Rate ◽  
Interleukin 2 ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Cross Resistance ◽  
High Dose ◽  
Phase Iii Trial ◽  
Effector Cells ◽  
To Receive

Abstract The CALGB evaluated the use of rIL-2 for immunotherapy of minimal residual disease in a phase III trial in patients with AML in first CR after completing all planned chemotherapy. The rationale supporting the use of rIL-2 in this setting includes its ability to effect antigen-independent cytotoxicity against AML blasts, its non-cross resistance with cytotoxic agents, and its ability to expand cytotoxic T and natural killer (NK) cells. Pts &lt; 60 years with untreated non-M3 AML were eligible. 734 patients were enrolled. The first 302 patients were randomized between 2 induction regimens: Ara-C, Daunorubicin, and Etoposide (ADE) or ADEP with the P-glycoprotein modulator PSC-833 (Kolitz et al, ASH 2005). The remaining 432 patients received ADE induction. Post-remission therapy was based on cytogenetic risk factors: patients with Core Binding Factor (CBF) AML received 3 courses of High-Dose Ara-C (HiDAC), while all others were assigned to receive a 2 step autologous transplant (ASCT) regimen (Linker et al, Biol Blood Marrow Transpl 2000). Randomization between rIL-2 and observation was to occur no later than 120 days after day 1 of the last HiDAC cycle or day 0 of ASCT, as soon as the neutrophil count &gt; 750/μl, platelets &gt; 50,000/μl with bone marrow showing a leukemia-free state and trilineage maturation and recovery from non-hematological toxicity to &lt; grade 2. The 90 day immunotherapy regimen consisted of low-dose rIL-2 sequences for expanding cytotoxic effector cells and brief, higher dose bolus treatments aimed at activating them. rIL-2 was given SC at 1 x 106 IU/m2 on days 1–14, 19–28, 33–42, 47–56, 61–70 and 75–90, and 12–15 x 106 IU/m2 on days 15–17, 29–31, 43–45, 57–59 and 71–73. CR was achieved in 77% of evaluable patients. After HiDAC consolidation or ASCT, patient refusal, early relapse, and delayed blood count recovery accounted for nearly all failures to undergo randomization to IL-2 or observation. The distribution of patients with CBF and non-CBF AML was comparable between the randomized arms. The median follow-up time from the post-remission randomization date for the surviving patients is 29 months. By intention-to-treat, for the 214 randomized patients, the 3-year disease-free survival rate is 45% (95% CI: 35%, 56%) on the observation arm and 56% (47%, 67%) on the rIL-2 arm (p=0.11; logrank test); the 3-year overall survival rate is 61% (52%, 72%) for patients randomized to observation and 68% (58%, 79%) for the rIL-2 arm (p=.0.09). Twenty-nine of the 107 patients randomized to rIL-2 therapy either refused to receive rIL-2 or were unable to start because of unresolved toxicities; another 28 patients started treatment but failed to complete their 90-day course. Grade 4 toxicities were neutropenia (17%), thrombocytopenia (11%), febrile neutropenia (FN, 1%), increased bilirubin (1%) and hypocalcemia (1%). Grade 3 toxicities, observed in 10%–14% of patients, were hypotension, fatigue, dehydration and FN. We conclude that post-consolidation immunotherapy with 90 days of rIL-2 is tolerable but not well accepted by patients and/or physicians. Further follow-up and additional analyses are planned, correlating outcomes with clinical subsets, amount of rIL-2 therapy received, as well as measurements of ex vivo cytotoxicity mediated by patients’ effector cells against cryopreserved autologous AML blasts.

Consolidation with Alemtuzumab Improves Progression-Free Survival in Patients with Chronic Lymphocytic Leukemia (CLL) in First Remission - Long-Term Follow-Up of a Randomized Phase III Trial of the German CLL Study Group (GCLLSG).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 33-33 ◽  
Author(s):  
C. Schweighofer ◽  
M. Ritgen ◽  
B. Eichhorst ◽  
R. Busch ◽  
M. Kneba ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
First Line ◽  
Phase Iii Trial ◽  
Free Survival ◽  
To Receive ◽  
Line Chemotherapy

Abstract Purpose: Alemtuzumab (MabCampath) is a humanized monoclonal antibody that targets the CD52 antigen, which is highly expressed on most human B and T lymphocytes. Alemtuzumab has shown considerable activity in both relapsed/refractory CLL and in the frontline treatment setting. In a recent study, treatment with single-agent alemtuzumab induced MRD-negative remissions in 20% of patients with relapsed/refractory CLL (Moreton et al JCO 2005;23:2971–2979). Other studies suggest that MRD negativity can also be attained when alemtuzumab is administered as consolidation for patients with CLL who achieve incomplete initial responses to chemotherapy. Here, we report our long-term experience within a randomized phase III trial that investigates the role of alemtuzumab for consolidation therapy in patients with previously untreated CLL. Methods: Pts in complete or partial remission after induction chemotherapy, with either fludarabine (F) or fludarabine plus cyclophosphamide (FC), were randomized to receive either alemtuzumab 30 mg, 3 times a week for ≤12 wks or no further treatment. Of 21 eligible pts, who had responded to induction with F or FC (1 CR, 1 nPR, 9 PRs), 11 pts (median age: 60 years) randomized to receive alemtuzumab consolidation and 10 to the observation arm. Pts in the alemtuzumab arm received standard premedication and infection prophylaxis with famciclovir and trimethoprim/sulfamethoxazole. Results: After a median follow-up of 48 months, calculated from time of randomization within this consolidation trial, progression-free survival (PFS) was significantly improved for pts who received alemtuzumab consolidation compared to those who received no further treatment (median PFS not reached versus 20.6 months, P = 0.004). PFS from the beginning of induction therapy with F or FC is also significantly greater for patients in the alemtuzumab consolidation arm versus the observation arm. So far, 3 of 11 pts presented with disease progression after alemtuzumab consolidation compared with 8/10 progressing pts in the observation arm. Differences in PFS between both arms were not associated with disease stage before first line treatment, type of first line chemotherapy (F vs. FC) or response status before initiation of consolidation therapy (CR vs. nPR vs. PR). Correlations between achievement of MRD negative responses and PFS is still under investigation and is planned for presentation. With the exception of 2 patients (1 pt in each arm) all patients remain alive. The study was stopped prematurely due to severe infections (7 CTC III infections, which included 4 CMV reactivations, 1 CTC IV infection) in 7/11 patients being treated with alemtuzumab. However, these infections were successfully treated, not associated with the cumulative dose of alemtuzumab, and no late complications of consolidation therapy have been observed. Conclusions: Although based on few pts due to incomplete accrual, long-term PFS was significantly prolonged in patients with CLL receiving alemtuzumab consolidation after first line chemotherapy with F or FC. An ongoing phase I/II trial of the GCLLSG (CLL2i) is currently evaluating the optimal dose and schedule of alemtuzumab in CLL pts after fludarabine-based chemotherapy.

Bevacizumab (Bev) in combination with XELOX or FOLFOX4: Updated efficacy results from XELOX-1/ NO16966, a randomized phase III trial in first-line metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4028-4028 ◽  
Author(s):  
L. Saltz ◽  
S. Clarke ◽  
E. Diaz-Rubio ◽  
W. Scheithauer ◽  
A. Figer ◽  
...  
Keyword(s):  
Survival Data ◽  
Progressive Disease ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Phase Iii Trial ◽  
Independent Review ◽  
Line Setting ◽  
To Receive

4028 Background: NO16966 is the first phase III trial to evaluate the combination of Bev with oxaliplatin-based chemotherapy (FOLFOX4 or the XELOX regimen) in the first-line setting. Methods: 1401 pts were randomized to receive FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) or XELOX (oxaliplatin 130mg/m2 iv, capecitabine 1000mg/m2 bid oral d1–14, q3w) plus Bev (5mg/kg q 2 weeks for FOLFOX, 7.5mg/kg q 3 weeks for XELOX) or Placebo in a 2x2 factorial design. Results: The addition of Bev to oxaliplatin-based chemotherapy demonstrated a significant benefit in terms of PFS in the primary analysis (HR 0.83; 97.5% CI 0.72- 0.95, p=0.0023). Prespecified analysis of PFS on treatment (defined as progressive disease or death within 28 days from the last dose of study treatment) and PFS analysis based on tumor assessments by an independent review committee (IRC) were consistent with the benefit observed in the primary analysis. PFS results are shown in Table 1 . 34% of patients have died and the median follow-up for survival at this time is 18.6 months. Mature overall survival data will be presented at the meeting. Conclusions: This large, international phase III trial demonstrates that the addition of Bev to oxaliplatin-based chemotherapy regimens significantly improves PFS. [Table: see text] [Table: see text]

Update of AMC 0101 study: A phase III trial of intraperitoneal cisplatin and early mitomycin-C plus long-term doxifluridine plus cisplatin (iceMFP) versus mitomycin-C plus short-term doxifluridine (Mf) as adjuvant chemotherapy for grossly serosa-positive advanced gastric cancer (NCT00296322).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Yoon-Koo Kang ◽  
Baek-Yeol Ryoo ◽  
Heung-Moon Chang ◽  
Dae Young Zang ◽  
Tae Won Kim ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Mitomycin C ◽  
Stage I ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Early Start ◽  
Intent To Treat ◽  
To Receive

4 Background: To improve the adjuvant chemotherapy in serosa-involving AGC, we adopted intraperitoneal and early start of chemotherapy, as well as prolongation of fluoropyrimidine and addition of cisplatin (P) to Mf regimen. The primary efficacy results of AMC0101 study on 3y relapse free survival rate (RFSR) were presented in 2008 ASCO. Now, we update the results with longer follow up. Methods: Pts with serosa-positive AGC who underwent curative resection were randomized to receive either Mf or iceMFP. Pts with postoperative stage I or IV (M1) were excluded. For Mf, 20 mg/m2 of mitomycin-C (M) was injected 3-6 wks after surgery and 4 wks later, 460-600 mg/m2/day of doxifluridine was administered orally for 3 months. For iceMFP, 100 mg of P was administered intraperitoneally for 2 h during surgery and 15 mg/m2 of M was injected 1 day after surgery. Doxifluridine was started 4 wks after surgery and extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of P were added. Results: Between Oct 2001 and Apr 2007, 640 pts were randomized (318 in Mf, 322 in iceMFP). One hundred and nineteen pts (60 in Mf, 59 in iceMFP) were excluded (postoperative stage I in 90, M1 in 13, positive resection margin in 10, and others in 6). Therefore, a total of 521 pts (258 in Mf, 263 in iceMFP) were eligible for intent-to-treat analysis. Postoperative stages were II in 33.4%, IIIA in 31.9%, IIIB in 17.5%, and IV in 17.3% of pts. As of April 2011, with a median follow-up of 6.6 years, iceMFP group had a significantly longer RFS (HR, 0.73; 95% C.I. 0.57 - 0.93; p=0.0092) and overall survival (HR, 0.77; 95% C.I. 0.60 - 0.98; p=0.0365) than Mf group. Conclusions: We could confirm with longer follow up that benefit in 3y RFSR from iceMFP could be translated into benefit in 5y OSR. Considering no benefit of adding cisplatin and prolongation of doxifluridine to Mf chemotherapy in curatively resected AGC pts (AMC 0201), intraperitoneal cisplatin and/or early start of chemotherapy seemed to be responsible for the improved efficacy of iceMFP chemotherapy in this study.

scholarly journals Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005

2015 ◽  
Vol 33 (34) ◽  
pp. 4093-4098 ◽  
Author(s):  
Yongli Ji ◽  
Cathryn Rankin ◽  
Steven Grunberg ◽  
Andy E. Sherrod ◽  
Jamshid Ahmadi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progesterone Receptors ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Term Administration ◽  
To Receive

Purpose Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma. Patients and Methods Eligible patients were randomly assigned to receive either mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug. Results Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival. Conclusion Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma.

P136 Efficacy and safety of olokizumab in a phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Eugen Feist ◽  
Saeed Fatenejad ◽  
Sergey Grishin ◽  
Elena Korneva ◽  
Michael Luggen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Inhibitor Therapy ◽  
Phase Iii ◽  
Major Adverse Cardiovascular Events ◽  
Research Support ◽  
Acr20 Response ◽  
Phase Iii Trial ◽  
Tnf Α ◽  
To Receive

Abstract Background/Aims  Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6. Here we present the results of the phase III study of OKZ in anti-TNF-IR patients. Methods  Patients with moderately to severely active RA who had previously failed TNF inhibitors (ClinicalTrials.gov Identifier NCT02760433/CREDO3) were randomized in a 2:2:1 ratio to receive subcutaneous (SC) injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or placebo (PBO), plus MTX. At week 16, all subjects in the PBO group were randomized in a 1:1 ratio to receive either of OKZ regimes. The primary endpoint was ACR20 response at week 12. Results  368 subjects were randomised according to the protocol and 320 patients (87%) completed the 24-week treatment period. Baseline characteristics were comparable across arms. Both regimens of OKZ were significantly better in primary endpoint: ACR20 were 60.9% (p = 0.0029 in comparison vs. PBO) in OKZ q2w, 59.6% in OKZ q2w (p = 0.0040 in comparison vs. PBO) and 40.6% in PBO. The key efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidences of treatment-emergent adverse events (TEAE) were 65.5% in OKZ q2w, 65.0% in OKZ q4w and 50.7% in PBO. Subsequent randomization of PBO arm at week 16 did not change TEAEs incidence rate per treatment group significantly: 64.3% in any OKZ q2w and 59.7% in any OKZ q4w. The majority of TEAEs in all groups were not serious and were of mild or moderate severity. Incidence of treatment-emergent serious adverse events (TESAE) were: 12 (7.0%) subjects in any OKZ q2w; 6 subjects (3.2%) in any OKZ q4w group, all in the first 16 weeks. The most frequently reported TESAEs across all treatment groups were infections and infestations: 2 (1.2%) in OKZ q2w group, 2 (1.1%) in OKZ q4w group. No opportunistic infections including active tuberculosis, major adverse cardiovascular events, gastrointestinal perforations or deaths were reported. Conclusion  In this global Phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs and symptoms of RA compared to PBO plus MTX over a 24-week period. Treatment with OKZ q2w and q4w in this difficult to treat population was well tolerated and consistent with the established safety profile of anti-IL-6 agents. Disclosure  E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. M. Luggen: Consultancies; Amgen, Sun Pharmaceuticals, R-Pharm International. Grants/research support; I havAbbvie, R-Pharm, Sun Pharmaceuticals, Pfizer, Novartis, Lilly, and GSK. E. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

Betulin wound gel accelerated healing of superficial partial thickness burns: Results of a randomized, intra‐individually controlled, phase III trial with 12‐months follow‐up

Burns ◽  
2019 ◽  
Vol 45 (4) ◽  
pp. 876-890 ◽  
Author(s):  
Quentin Frew ◽  
Hans-Oliver Rennekampff ◽  
Peter Dziewulski ◽  
Naiem Moiemen ◽  
Tobias Zahn ◽  
...  
Keyword(s):  
Phase Iii ◽  
Phase Iii Trial ◽  
Partial Thickness ◽  
Partial Thickness Burns

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

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