Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy.

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

North American Cancer Center Clinical Research Capacity and Benchmarking in the Postpandemic Era.

Purpose: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here.

The Glass Wall: Gendered Authorship Disparities in CD 19 and BCMA CAR-T Clinical Trials for Lymphoma and Myeloma.

Introduction: Existing literature suggests that women are significantly underrepresented in the field of hematology-oncology. Women make up 35.6% of hematologists and data on females as site investigators for pivotal trials and authors in publications of pivotal trials in hematologic malignancies, specifically in the novel niche of Chimeric antigen receptor T cell (CAR-T), is sparse.

Evaluating the impact of delayed study startup on accrual in cancer studies.

Background: Drug development in cancer medicine depends on high-quality clinical trials, but these require large investments of time to design, operationalize, and complete; for oncology drugs, this can take 8-10 years. Long timelines are expensive and delay innovative therapies from reaching patients. Delays often arise from study startup, a process that can take 6 months or more.

Using Bayesian hierarchical modeling for performance evaluation of clinical trial accrual for a cancer center.

Introduction: Slow patient accrual in cancer clinical trials is always a concern. In 2021, the University of Kansas Comprehensive Cancer Center (KUCC), an NCI-designated comprehensive cancer center, implemented the Curated Cancer Clinical Outcomes Database (C3OD) to perform trial feasibility analyses using real-time electronic medical record data. In this study, we proposed a Bayesian hierarchical model to evaluate annual cancer clinical trial accrual performance.

The approach of HMA plus VEN with or without BMT for all patients with AML.

Treatment options for acute myeloid leukemia (AML) have expanded over the last 5 years. New regimens are increasing the options for patients who previously may not have been offered any antineoplastic therapy. The use of the hypomethylating agent (HMA) decitabine or azacitidine combined with the BCL2 inhibitor venetoclax (HMA-VEN) has improved overall survival in an older and unfit population compared to HMA therapy alone.

A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML.

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS).

A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML.

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine.

Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia.

PLK1 is overexpressed in acute myeloid leukemia (AML). A phase 1b trial of the PLK1 inhibitor onvansertib (ONV) combined with decitabine (DAC) demonstrated initial safety and efficacy in patients with relapsed/refractory (R/R) AML. The current study aimed to identify molecular predictors of response to ONV + DAC in R/R AML patients.

Multi-institutional analysis of outcomes in acute myeloid leukemia patients with central nervous system involvement.

We evaluated outcomes of AML patients with central nervous system (CNS) involvement at two academic institutions. Fifty-two adult patients were identified. Neurologic symptoms were reported in 69% of patients, with headache the most common (33%).

Quantifying the impact of the COVID-19 pandemic on cancer center clinical trial operations.

Background: Oncology clinical trials are complex, and the COVID-19 pandemic caused major disruptions in 2020.

Methods: Using its networking and sharing of best practices, the Association of American Cancer Institutes, comprising 105 cancer centers, solicited a longitudinal series of voluntary surveys from members to assess how clinical trial office operations were affected. The surveys showed that centers were able to keep oncology trials available to patients while maintaining safety.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

Background: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.

Methods: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.

Bolstering the complex study start-up process at NCI cancer centers using technology.

Background: The study startup process for interventional clinical trials is a complex process that involves the efforts of many different teams. Each team is responsible for their startup checklist in which they verify that the necessary tasks are done before a study can move on to the next team. This regulatory process provides quality assurance and is vital for ensuring patient safety [10].

Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial.

CPX-351 (Europe: Vyxeos liposomal; United States: Vyxeos) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 improved the remission frequency, overall survival, and post-transplant survival versus 7 + 3. This post hoc analysis evaluated the final 5-year follow-up outcomes according to the European LeukemiaNet 2017 risk classification.

Integrative analysis of drug response and clinical outcome in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity with genomic, transcriptomic, and clinical annotations for a large cohort of AML patients, which facilitated discovery of functional genomic correlates. Here, we present a dataset that has been harmonized with our initial report to yield a cumulative cohort of 805 patients (942 specimens).

Gender disparities in the National Institutes of Health funding for hematologic malignancies and cellular therapies.

We investigated gender inequality in the National Institutes of Health (NIH) funding for hematologic malignancies and cellular therapies (HMCT). The data were retrieved from the NIH Research Portfolio Online Reporting Tools (RePORT). In 2018-2019, 1834 grants totaling $799 million were awarded (men 71% vs.

Analysis of Pharmacodynamics and Single-Agent Activity of CD3xCD123 Bispecific Antibody APVO436 in Relapsed/Refractory AML and MDS Resistant to HMA or Venetoclax Plus HMA.

APVO436 is a recombinant bispecific antibody designed to direct host cytotoxic T-cells to CD123-expressing blast cells in patients with hematologic malignancies. APVO436 showed promising tolerability and single-agent activity in relapsed or refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary purpose of this analysis was to evaluate the therapeutic and pharmacodynamic effects of APVO436 in 14 R/R AML/MDS patients who had failed treatment with hypomethylating agents (HMA) or venetoclax plus HMA prior to being enrolled in the APVO436 Phase 1 dose-escalation study that was recently completed.