A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia.

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator.

In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management.

Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible patients with newly diagnosed MM to receive all-oral ixazomib-lenalidomide-dexamethasone (IRd; ≤39 cycles or until progression or toxicity) following three cycles of bortezomib-based induction. Primary endpoint: 2-year progression-free survival (PFS).

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

Background: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies.

Methods: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA.

Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib.

Background: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes.

Patients And Methods: US community sites are enrolling non-transplant-eligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39 cycles or until progression or toxicity). The patients use mobile or wearable digital devices to collect actigraphy (activity and sleep) data and electronically complete HRQoL, treatment satisfaction and medication adherence questionnaires.

Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib.

Background: Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown.

Methods: This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib.

Temporal evolution of patient characteristics enrolled on phase I trials.

Purpose: Phase I trials serve a crucial role in anticancer drug development. Given the explosion in the number of both approved anticancer therapies and agents in development, we hypothesized that the characteristics of patients enrolling on phase I clinical trials is evolving.

Patients And Methods: We reviewed 476 published phase I trials over the past decade encompassing 15,100 patients and determined the following characteristics for patients enrolled: age; percentage with ECOG PS of 0, 1, or 2; sex; race; and number of prior chemotherapeutic therapies received: 0, 1, 2 or ≥ 3.

A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumors.

Rebeccamycin analog (RA) is an antitumor antibiotic with both topoisomerase I and II inhibiting activity. Topoisomerase inhibitors have demonstrated synergy with platinum agents. We performed a phase I trial of combination RA with oxaliplatin in patients with refractory solid tumors.

Multi-institutional phase I trials of anticancer agents.

Purpose: Physicians involved in the conduct of phase I studies of novel anticancer agents have raised concerns about the emergence of multi-institutional phase I trials and about using the optimal biologic dose (OBD) as an alternative to the maximum-tolerated dose (MTD) as the primary end point in early drug development. We sought to determine the factors associated with multi-institutional phase I studies and OBD determination.

Patients And Methods: We reviewed all published phase I trials between January 1998 and June 2006 from two major clinical cancer journals.