Prolymphocytic Leukemia

P1, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P1, N=32, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Phase classification: P1a/1b --> P1

P1, N=36, Recruiting, Sumithira Vasu | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.

P2, N=25, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=37, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=62 --> 19

Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab...Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.

P1, N=69, Active, not recruiting, Acerta Pharma BV | Phase classification: P1b --> P1

Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms.

© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

P2, N=135, Active, not recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2024

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

We review the diagnostic criteria including clinical, immunophenotypic and molecular characteristics of patients with HCL-V and other HCL-like disorders including HCL, SDRPL, SMZL, B-PLL and the Japanese form of HCL. We also discuss the different criteria allowing us to separate these different entities and we will update the recent therapeutic options that have emerged, in particular the advances with chemoimmunotherapy and/or targeted therapies.

This study identified a circBCAR3-miR-27a-3p-SLC7A11 axis regulating ferroptosis and peroxidation of B-prolymphocytic leukaemia cells which might be a key mechanism facilitating the survival of tumour cells. However, further validation based on more diverse cell lines and animal models might be required.

Introduction: T-Cell Prolymphocytic Leukemia (T-PLL) is a rare, aggressive T-cell malignancy with very poor prognosis. No substantial differences in T-PLL response rates or survival were observed when using the TPLL-ISG criteria when compared to historical reports. Patients who had a CR or CRi to alemtuzumab that proceeded with allo-SCT had a significantly prolonged OS and PFS. Patients with CD4-CD8+ T-PLL had inferior survival , but this will need to be validated in a larger sample set.

It describes key genetic alterations and their clinical implications. It also proposes recommendations on cytogenetic methods for MTNKN diagnosis.

P2, N=36, Recruiting, Ascentage Pharma Group Inc. | Phase classification: P2a --> P2 | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024

P2, N=60, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2023 --> Oct 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

Therefore, SUPT11 cells (used as a model of T-PLL) were exposed to venetoclax (25 and 50nM; BCL-2inh), fadraciclib (25 and 50nM; CDK2/9inh – indirect inhibitor of MCL-1 as it decreases mRNAs with high decay rates including MCL1 and MYC) or a combination of venetoclax and fadraciclib. In conclusion, preclinical evaluation of a T-PLL cell line and primary patient samples demonstrate BCL2-family dependency that can be effectively targeted with small molecule inhibitors of BCL2 and CDK2/9. In vivo studies in PDX models of T-PLL are underway to form the basis for clinical trials to study these combinations.

The emerging clinical data demonstrate that KT-333 is a potent degrader of STAT3 as demonstrated in PBMCs at doses that are well tolerated. These data provide the first evidence of STAT3 targeted protein degradation in humans with associated STAT3 pathway inhibition, along with potential early signs of antitumor activity, highlighting the potential of heterobifunctional degraders for targeting previously undruggable transcription factors implicated in diseases. Based on non-clinical data and PK/PD modeling, the high levels of degradation achieved so far are expected to be clinically efficacious in STAT3-dependent malignancies.

P1b, N=69, Active, not recruiting, Acerta Pharma BV | Trial completion date: Aug 2026 --> Sep 2027

P1, N=54, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P2, N=156, Completed, Masonic Cancer Center, University of Minnesota | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> May 2023

Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.

P=N/A, N=1000, Recruiting, Memorial Sloan Kettering Cancer Center

P1, N=52, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

A portion of patients can be cured with alemtuzumab induction followed by allogeneic hematopoietic stem cell transplant, but patients who relapse after transplant have a poor prognosis, and there is no standard of care. We report a case of a 64-year-old man with relapsed JAK3-mutant T-PLL following allogeneic transplant who was treated with ruxolitinib and venetoclax. Treatment with ruxolitinib and venetoclax resulted in a partial response including stabilization of the peripheral lymphocyte count, improvement in thrombocytopenia, decrease in splenomegaly, and a numerical reduction in the percentage of bone marrow involved by T-PLL. The combination was well tolerated with the exception of neutropenic infections. This case adds to the growing body of literature supporting venetoclax and rituximab as a viable treatment option for relapsed/refractory T-PLL with JAK-STAT alterations.

P1/2, N=306, Active, not recruiting, Acerta Pharma BV | Trial completion date: Jul 2026 --> Sep 2027

No abstract available

P1a/1b, N=32, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

P2, N=208, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

Among 52 patients with hematological malignancies the maximum tolerated dose (MTD) was not reached and no clinical TLS was observed.20 In this study of 22 evaluable patients with RR CLL there was an overall response rate (ORR) of 63.6% (14/22).20 A larger study of 114 patients with RR CLL evaluated lisaftoclax in combination with either the Bruton's tyrosine kinase inhibitor (BTKi) acalabrutinib or the anti CD20 monoclonal antibody rituximab (NCT04215809)...In CLL an overall response rate (ORR) to BGB-1147 of 100% as monotherapy was observed among 8 patients with RR disease.25 In 12 patients with RR MM, the ORR to BGB-1147 in combination with dexamethasone varied from 0–68% depending on the dose cohort.26 In combination with azacytidine in AML the ORR to BGB-11417 was 74% among those with treatment naïve (TN) disease (n=20/27) and 65% (n=13/20) in the cohort with RR disease.27 BGB-11417 monotherapy in 23 patients with RR NHL demonstrated responses in 2 patients with diffuse large B cell lymphoma (DLBCL) and one patient with marginal zone lymphoma (MZL).28 In 11 patients with RR MCL treated with BGB-11417 in combination with zanubrutinib there was a 55% (6/11) ORR.28 S55746 is a potent BAX/BAK dependent BCL2 inhibitor administered orally.18,29 Developed by Servier, it has been tested in phase I studies in CLL, NHL and AML. In a study of S55746 among 37 patients with RR NHL, no dose limiting toxicities (DLT) or TLS was observed after a medium duration of treatment of 42 days.30 FCN-338 is another orally available selective BCL2 inhibitor developed by Fochon currently undergoing phase I testing in RR CLL.18,31 Clinical outcomes with this drug are yet to be publicly reported...More recently navitoclax has been tested in RR myelofibrosis (MF) in combination with ruxolinitib with evidence of clinical response to the combination.35 AZD0466 by Astrazeneca is a nanomedicine potent dual BCL2/ BCLxL inhibitor that mediates BAX/BAK induced apoptosis36,37 and is administered intravenously...Among 9 patients reported undergoing testing for RR hematological malignancy the DLT had not yet been reached.38 Pelcitoclax or APG1252 by Ascentage is a more recent BAX/BAK dependent dual BCL2 and BCLxL inhibitor18,39,40 currently in phase I trials in RR NHL (NCT05186012)...There are multiple emerging BCL2 inhibitors currently undergoing clinical trial testing in hematological malignancies, and it remains too early to appreciate the differential efficacy and toxicity profiles that these agents may carry compared with venetoclax. It is hoped that the results seen with venetoclax can be improved upon across a raft of disease groups over the coming years.

The workshop highlighted complexity of progression and transformation in CLL/SLL and B-PLL, as well as diagnostic caveats accompanying heterogeneous presentations of RT and other manifestations of disease progression. Molecular genetic studies are pivotal for diagnosis and determination of clonal relationship, and to predict response to treatment and identify resistance to targeted therapy.

P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=62, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024