Publications by authors named "Klencke B"
Article Synopsis
- JAK inhibitors are the main treatment for myelofibrosis, but they often overlook anemia and may even make it worse.
- The authors discuss their findings from phase III trials of momelotinib, the first FDA-approved treatment for myelofibrosis patients with anemia, to demonstrate how varying criteria can affect reported benefits related to anemia.
- They suggest forming an expert consensus panel to standardize the definition of anemia-related responses in myelofibrosis treatment to improve consistency and clarity in clinical trial reporting.
Article Synopsis
- - Patients with myelofibrosis suffer from various symptoms due to bone marrow fibrosis and inflammation, and improving these symptoms can enhance their quality of life.
- - This study analyzed data from two phase III trials of momelotinib (SIMPLIFY-1 and SIMPLIFY-2) to determine a meaningful change threshold (MCT) for symptoms, finding it to be 8 points for treatment-naive patients and 6 points for those previously treated.
- - Results showed that momelotinib effectively improved patient symptoms, suggesting that the traditional 50% reduction standard used in clinical trials may be too conservative and that momelotinib offers significant benefits compared to other treatments in myelofibrosis patients.
Article Synopsis
- Momelotinib, an oral JAK inhibitor, showed positive results in treating intermediate- and high-risk myelofibrosis (MF), benefiting symptoms, spleen size, and anemia.
- Post hoc analyses from three phase 3 studies evaluated momelotinib's effectiveness and safety in patients with low platelet counts (<100 × 10/L), revealing comparable or superior response rates to ruxolitinib, especially in transfusion independence.
- Overall, momelotinib maintained treatment benefits and a consistent safety profile in thrombocytopenic patients, presenting itself as a promising option for managing MF in this population.
Article Synopsis
- - The MOMENTUM study successfully showed that momelotinib, compared to danazol, provided significant improvements in symptoms, spleen size, and anemia in myelofibrosis patients at the 24-week mark, and this analysis focuses on outcomes from 24 to 48 weeks.
- - The study involved 107 international sites with adult patients who had a history of myelofibrosis and were treated with a Janus kinase inhibitor, with participants randomly assigned to receive either momelotinib or danazol for 24 weeks.
- - After 24 weeks, all patients transitioned to open-label momelotinib, and this updated analysis reports on the duration of responses and additional patient results through week 48
Article Synopsis
- This study was a Phase 1/2 trial evaluating the novel drug SRA737, a checkpoint kinase 1 inhibitor, for patients with advanced solid tumors, focusing on its safety and dosage.
- A total of 107 patients were treated, determining the maximum tolerated dose to be 1000 mg daily, with mild to moderate side effects like diarrhea and nausea; however, no significant tumor responses were observed.
- The findings suggest that while SRA737 is generally well tolerated, its effects as a single agent are limited, indicating it may be more effective when used in combination with other therapies.
Article Synopsis
- Myelofibrosis (MF) causes significant health-related quality of life issues, and traditional clinical trials often use a basic measure of symptom improvement, which may not capture the full range of patient experiences.
- This study used advanced statistical methods to analyze how symptoms change over a 24-week period in patients with MF treated with momelotinib, comparing these changes to a control group.
- Results showed that both momelotinib and ruxolitinib improved overall symptoms, but momelotinib consistently led to better outcomes, with more patients reporting improvements or stability compared to the control group.
Article Synopsis
- Momelotinib, a new treatment for myelofibrosis, shows promise by improving symptoms, spleen size, and anemia, unlike existing JAK inhibitors that primarily address symptoms and spleen enlargement.
- The MOMENTUM study is a global phase 3 trial comparing momelotinib to danazol in patients with symptomatic myelofibrosis who have previously been treated with JAK inhibitors.
- Results indicated that a higher percentage of patients treated with momelotinib experienced a significant reduction in their myelofibrosis-related symptoms compared to those on danazol.
Purpose: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737.
Patients And Methods: Patients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16, and 17, and intravenous gemcitabine on days 1, 8, and 15.
Article Synopsis
- Janus kinase inhibitors (JAKi) improve symptoms and spleen size in myelofibrosis but don't address anemia, which is linked to worse outcomes.
- Momelotinib shows promise in improving anemia, symptoms, and spleen size, with survival rates similar to ruxolitinib in clinical trials.
- Achieving transfusion independence is crucial for better survival outcomes, highlighting momelotinib's potential as a treatment option for myelofibrosis patients.
Background: PNT2258 is a liposomal formulation that encapsulates multiple copies of PNT100, a native, chemically unmodified, 24-base DNA oligonucleotide designed to target the regulatory region upstream of the B-cell lymphoma 2 (BCL2) gene.
Methods: This phase II, multicenter, single-arm, open-label, 2-stage design study investigated the single-agent activity of PNT2258 in patients with relapsed/refractory DLBCL. Initially, patients had to have a performance status (PS) of ≤2 and prior exposure to CD20-targeted therapy, an alkylating agent, and a steroid with no upper limit.
A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies.
Clin Lymphoma Myeloma Leuk
December 2021
Background: PNT2258 consists of a native, chemically unmodified, 24-base DNA oligonucleotide designed to target the regulatory region upstream of the BCL2 gene, delivered in a protective liposome. Derangement of BCL2-regulated control mechanisms is a defining characteristic of certain malignancies, and it was hypothesized that the oligonucleotide would promote anticancer activity via suppression of BCL2 transcription.
Methods: PNT2258 was evaluated in this, multicenter, nonrandomized, open-label Phase 2 study in 13 participants with relapsed/refractory B-cell malignancies to investigate potential antitumor activity and safety.
An operationalized workflow paradigm is presented and validated with pilot subject data. This approach is reproducible with a high concordance rate between individual readers (kappa 0.73 [confidence interval 0.
View Article and Find Full Text PDFBackground: Carfilzomib is a next-generation proteasome inhibitor with single-agent activity in patients with relapsed and refractory multiple myeloma (R/R MM). In PX-171-003-A1, a single-arm phase 2 study of carfilzomib monotherapy in heavily pretreated patients, the overall response rate was 23.7%, 37% of patients achieved ≥ minimal response and median overall survival (OS) was 15.
View Article and Find Full Text PDFTrastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate in development for treatment of HER2-positive cancers. T-DM1 has been tested as a single agent in a phase I and 2 phase II studies of patients with heavily pretreated metastatic breast cancer (MBC), with the maximum tolerated dose established at 3.6 mg/kg intravenously for every-3-week dosing.
View Article and Find Full Text PDFPurpose: The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2)-overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population.
View Article and Find Full Text PDFErlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is active in glioblastoma. We evaluated erlotinib efficacy in patients with first-relapse glioblastoma and assessed whether response was related to EGFR amplification and/or concomitant use of enzyme-inducing antiepileptic drugs (EIAEDs) in a phase II open-label study of glioblastoma patients in first relapse. Patients took erlotinib daily until progression.
View Article and Find Full Text PDFPurpose: To determine whether therapy with a DNA methyltransferase inhibitor is effective in achieving demethylation and gene re-expression in tumor DNA in patients.
Methods: Biopsy specimens were obtained from patients with Epstein-Barr virus-associated tumors, enrolled on a clinical trial of 5-azacitidine, within 72 hours of the conclusion of the last infusion of the first cycle of therapy, and compared to pretreatment specimens. Methylation-specific polymerase chain reaction, bisulfite genomic sequencing, and immunohistochemistry were used to assess demethylation and gene re-expression.
Background: 131I-Metaiodobenzylguanidine (131I-MIBG) can be used systemically to treat malignant pheochromocytoma. To improve outcome, the authors used higher levels of activity of 131I-MIBG than previously reported. The authors reported the response rates and toxicity levels in patients with malignant pheochromocytoma or paraganglioma who were treated with high-dose 131I-MIBG.
View Article and Find Full Text PDFAlthough not yet included in the Centers for Disease Control definition of AIDS, anal cancer clearly occurs more commonly in HIV-infected patients. An effective screening program for those groups who are at highest risk might be expected to impact rates of anal cancer just as significantly as did cervical Pap screening programs for the incidence of cervical cancer. Despite a relatively low rate of progression from AIN to invasive cancer, the scope of the problem is enormous based on the prevalence of anal HPV infection and the size of the HIV-infected, at-risk population.
View Article and Find Full Text PDFObjective: To determine whether the natural history of melanoma is different in patients who test positive for human immunodeficiency virus (HIV) compared with matched control subjects.
Design: Retrospective cohort analysis.
Setting: Ambulatory care at 2 university-affiliated medical centers.
Background: Conventional systemic chemotherapy currently available for patients with inoperable hepatocellular carcinoma is ineffective. The purpose of this study was to evaluate the safety and efficacy of eniluracil/5-fluorouracil (5-FU) in the treatment of patients with this highly refractory disease.
Patients And Methods: This multicenter, open-label study evaluated a 28-day oral regimen of 5-FU (1 mg/m2 twice daily) plus the dihydropyrimidine dehydrogenase inhibitor, eniluracil (10 mg/m2 twice daily), in patients with chemotherapy-naive or anthracycline-refractory inoperable hepatocellular carcinoma.
High-grade dysplasia induced by high-risk types of human papillomavirus (HPV) precedes invasive cancer in anal squamous epithelium just as it does in the cervix. A therapeutic HPV vaccine strategy as a potential treatment for anal dysplasia was tested in a standard Phase I dose escalation trial. The primary objective was to evaluate the safety of the agent; additional study aims were to evaluate the histological response, immune response, and effect on anal HPV-16 infection.
View Article and Find Full Text PDFDesign: A selection of primary and transformed cell types were evaluated for their susceptibility to infection with human herpesvirus 8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus.
Methods: Sources of HHV-8 included Kaposi's sarcoma lesion punch biopsies that were either cocultured directly with target cells or that were first cocultured with human lymphocytes to derive HHV-8-containing fluids that were inoculated onto target cells. HHV-8 was also obtained from primary effusion lymphoma-derived cell lines.