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Cancers
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Advances in Clinical Trials of Hematological Malignancies
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Advances in Clinical Trials of Hematological Malignancies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (15 June 2024) | Viewed by 4766

Special Issue Editor

Dr. Lajos Gergely

E-Mail Website
Guest Editor
Department of Hematology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Interests: lymphoma; bone marrow transplantation; cellular therapy; immune therapy; hematology

Special Issue Information

Dear Colleagues, 

During the last decade the therapy of hematologic malignancies has undergone a major expanse. Besides the conventional morfologic, immunophenotyping and cytogenetic data, we are able to perform next generation sequencing of multiple genes as well as methylation profile analyzis is possible to understand epigenetic dysregulations involved in these diseases. This large amount of information has provided us with new potential therapeutic targets, but we still have to fully understand and utilize this vast amount of information. The therapeutic utilization of chimeric receptor T and NK cells is also a rapidly expanding field achieving unprecedented results in previously refractory patients. The new clinical trials are often based on the so called "basket" approach to explore genetic and epigenetic subtypes of diseases responding to certain therapeutic agents. A special issue of this journal will focus on this field. We aim to publish papers on novel trials, or exploring novel targeted therapies as well as in vitro trials focusing on potential new therapeutic targets. 

Dr. Lajos Gergely
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lymphoma
  • leukemia
  • targeted therapy
  • cellular therapy
  • basket trial

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (2 papers)

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Research

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11 pages, 674 KiB  
Article
CPX-351 Pharmacokinetics and Safety in Adults with Hematologic Malignancies and Renal Function Impairment: Phase 1 Trial
by Scott R. Solomon, Bayard L. Powell, Jamie Koprivnikar, Catherine Lai, Heather Male, Laura C. Michaelis, Laura F. Newell, David Sanford, Jack Jenkins, Amy Zelaya, Sheryl Coppola, Stefan Faderl and Roland B. Walter
Cancers 2024, 16(5), 915; https://doi.org/10.3390/cancers16050915 - 24 Feb 2024
Viewed by 1217
Abstract
This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, [...] Read more.
This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment. Full article
(This article belongs to the Special Issue Advances in Clinical Trials of Hematological Malignancies)
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Review

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17 pages, 2033 KiB  
Review
Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care
by Mary Ann Anderson, Renata Walewska, Fidelma Hackett, Arnon P. Kater, Josie Montegaard, Susan O’Brien, John F. Seymour, Matthew Smith, Stephan Stilgenbauer, Ashley Whitechurch and Jennifer R. Brown
Cancers 2024, 16(5), 980; https://doi.org/10.3390/cancers16050980 - 28 Feb 2024
Viewed by 2905
Abstract
Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age [...] Read more.
Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax’s efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors’ clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL. Full article
(This article belongs to the Special Issue Advances in Clinical Trials of Hematological Malignancies)
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