Phase 2 Trial
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Diamant Thaçi ◽  
Bruce Strober ◽  
Kenneth B. Gordon ◽  
Peter Foley ◽  
Melinda Gooderham ◽  

Kavitha Ramaswamy ◽  
Peter Steinherz ◽  
Anurag K Agrawal ◽  
Christopher Jon Forlenza ◽  
Audrey Mauguen ◽  

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML) as outcomes remain poor. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory (R/R) AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate (ORR), defined as complete remission (CR) or CR with partial recovery of platelet count (CRp), was 71.4% (95%CI: 41.9 to 91.6%) for those patients in first relapse (n=14) and 47.4% ( 95%CI: 24.4 to 71.1%) for patients in 2nd or greater relapse or refractory disease. Responses were seen across multiple high risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year OS for patients in first relapse was 46.2% (95%CI: 19.1 to 73.3%) and 50.0% (95%CI: 26.9 to 73.1%) for patients who responded to TVTC. For pediatric and young adult patients with R/R AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.

2022 ◽  
Vol 12 (1) ◽  
Aleksandar Radosevic ◽  
Rita Quesada ◽  
Clara Serlavos ◽  
Juan Sánchez ◽  
Ander Zugazaga ◽  

AbstractMicrowave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5–4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66–5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.

Amer M. Zeidan ◽  
Isaac Wayne Boss ◽  
CL Beach ◽  
Wilbert B. Copeland ◽  
Ethan Greene Thompson ◽  

Azacitidine-mediated hypomethylation promotes tumor cell immune recognition but may increase inhibitory immune checkpoint (ICP) molecule expression. We conducted the first randomized phase 2 study of azacitidine plus the ICP inhibitor durvalumab versus azacitidine monotherapy as first-line treatment of higher-risk myelodysplastic syndromes (HR-MDS). Patients (N=84) received azacitidine 75 mg/m2 subcutaneously (days 1-7) with (Arm A) or without (Arm B) durvalumab 1500 mg intravenously on day 1 every 4 weeks. After a median follow-up of 15.25 months, 8 patients in Arm A and 6 in Arm B remained on treatment. Patients in Arms A and B received a median of 7.9 and 7.0 treatment cycles, respectively, with 73.7% and 65.9% completing ≥4 cycles. The overall response rate (primary endpoint) was 61.9% in Arm A (26/42) and 47.6% in Arm B (20/42; P=0.18), and median overall survival was 11.6 months (95% CI: 9.5, nonevaluable) versus 16.7 months (95% CI: 9.8, 23.5) (P=0.74). Durvalumab-related adverse events (AEs) were reported by 71.1% of patients; azacitidine-related AEs were reported by 82% (A) and 81% (B). Grade 3 or 4 hematologic AEs were reported in (Arm A vs B) 89.5% vs 68.3% of patients. Patients with TP53 mutations tended to have a worse response than patients without these mutations. Azacitidine increased PD-L1 (CD274) surface expression on bone marrow granulocytes and monocytes, but not blasts, in both arms. In summary, combining durvalumab and azacitidine in patients with HR-MDS was feasible, but with more toxicities and without significant improvement in clinical outcomes over azacitidine alone. NCT02775903

Piyush Chaudhary ◽  
Bharat Rathi ◽  
Renu Rathi ◽  
Vidushi Tyagi

Background: Non-alcoholic fatty liver disease (NAFLD), mostly diagnosed incidentally, is a rapidly emerging liver disorder. In absence of any specific treatment, current management focuses on theuse of hepatoprotective agents in addition to lifestyle modification and prevention of metabolic syndrome. Several Ayurveda agents have shown promising effects in patients over centuries of use. But this evidence needs to be assessed scientifically through reverse pharmacology approach. A polyingredient Ayurveda drug, Phalatrikadighanvati (PGV) has been selected for this study because of its long history of use and that its individual contents have shown positive results in liver disorders. Objective: Evaluation of efficacy of Phalatrikadighanvati in patients of non alcoholic fatty liver disease (NAFLD) along with its pharmaceutical and analytical study. Materials and Methods: The drug shall bepharmaceutically processed and analyzed as per pharmacopoeial standards.Present study has been designed as a randomized placebo controlled double blind clinical trial in two stages. The first stage shall be a pilot study to decide the best effective and safe dose in patients of NAFLD. The pilot study shall include two groups of 10 patients each in a dose of PGV 500mg and 1gm respectively twice a day for 12 weeks. After theselection of thebest dose, RCT will be conducted on that dose in the second stage.It shall be a Phase 2 trial with 60 patients divided equally in two groups.The patients in group one shall be given a dose as per the outcome of the pilot study twice a day and another group shall be administered placebo for a period of 12 weeks. Results: Efficacy of Phalatrikadi ghan vati will evaluated in terms of subjective and objective parameters using paired and unpaired t-test. Conclusion: PGV is expected to improve the diagnostic parameters in patients of NAFLD thus proving to be efficacious in managing NAFLDand act as a potent hepatoprotective agent.

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