scholarly journals A Prospective Phase 2 Clinical Trial of KIR Mismatched Unrelated Donor Transplantation for Children and Young Adults with High Risk AML: A Report of Children's Oncology Group AAML05P1 Study

2017 ◽  
Vol 23 (3) ◽  
pp. S134-S135
Author(s):  
Stella M. Davies ◽  
Robert Iannone ◽  
Todd Alonzo ◽  
Jim Wang ◽  
Robert Gerbing ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Young Adults ◽  
High Risk ◽  
Unrelated Donor ◽  
Phase 2 ◽  
Oncology Group ◽  
Phase 2 Clinical Trial ◽  
Prospective Phase ◽  
Children And Young Adults

scholarly journals Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis

2021 ◽  
Vol 5 (16) ◽  
pp. 3163-3173 ◽  
Author(s):  
Naveen Pemmaraju ◽  
Bing Z. Carter ◽  
Prithviraj Bose ◽  
Nitin Jain ◽  
Tapan M. Kadia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Objective Response ◽  
Severe Thrombocytopenia ◽  
Jak Inhibitor ◽  
Phase 2 ◽  
Jak Inhibitors ◽  
Phase 2 Clinical Trial ◽  
Smac Mimetics ◽  
Smac Mimetic

Abstract Outcomes in patients with high-risk and treatment-resistant myelofibrosis (MF) post-JAK inhibitor therapy remain poor, with no approved drug therapies beyond the JAK inhibitor class. In certain clinical situations, such as severe thrombocytopenia, administration of most JAK inhibitors are contraindicated. Thus, there is an unmet medical need for the development of novel agents for patients with MF. SMAC mimetics [or inhibitor of apoptosis (IAP) antagonists] induce apoptosis in cancer cells. Because these agents are hypothesized to have increased activity in a tumor necrosis factor-α cytokine-rich microenvironment, as is the case with MF, we conducted a single-center, investigator-initiated phase 2 clinical trial, with a monovalent SMAC mimetic LCL161 (oral, starting dose, 1500 mg per week) in patients with intermediate to high-risk MF. In an older group, 66% with ≥2 prior therapies and a median baseline platelet count of 52 × 103/μL and 28% with ASXL1 mutations, we observed a 30% objective response by Revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria. Notably, 6 responding patients achieved clinical improvement of anemia: 4, hemoglobin response; 2, transfusion independence. Median OS was 34 months (range, 2.2-60.1+). Reductions of cIAPs were observed in all responders. The most common toxicity was nausea/vomiting (N/V) in 64% (mostly grade 1/2); fatigue in 46%; and dizziness/vertigo in 30%. There were 4 grade 3/4 adverse events (2, syncope; 1, N/V; 1, skin eruption/pruritis). There were 2 deaths during the study period, both unrelated to the study drug. SMAC mimetics may represent an option for older patients with thrombocytopenia or for those in whom prior JAK inhibitors has failed. This trial was registered at www.clinicaltrials.gov as #NCT02098161.

Bendamustine: the remedy that came in from the cold

Blood ◽  
2014 ◽  
Vol 123 (7) ◽  
pp. 948-950 ◽  
Author(s):  
Suzanne Lentzsch
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
High Risk ◽  
Phase 2 ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Clinical Trial

In this issue of Blood, Ludwig and colleagues present the data of a phase 2 clinical trial showing that bendamustine, bortezomib, and dexamethasone (BBD) is a very active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma.1 More importantly, BBD overcomes the adverse prognosis in patients with high-risk cytogenetics.

scholarly journals Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

2016 ◽  
Vol 34 (20) ◽  
pp. 2380-2388 ◽  
Author(s):  
Eric C. Larsen ◽  
Meenakshi Devidas ◽  
Si Chen ◽  
Wanda L. Salzer ◽  
Elizabeth A. Raetz ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Dose Methotrexate ◽  
Children And Young Adults

Purpose Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival. Patients and Methods Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1. Results Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis. Conclusion High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.

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