- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Aromatic Nitrogen Mustard-Based Autofluorescent Amphiphilic Brush Copolymer as pH-Responsive Drug Delivery Vehicle. (Pubmed Central) - Jan 25, 2020
The present investigation reports the synthesis of a pH-responsive autofluorescent polymeric nanoscaffold for the administration of nonfluorescent aromatic nitrogen mustard chlorambucil (CBL) drug into the cancer cells...This property helped us intracellular tracking of CBL conjugated autofluorescent nanocarriers through fluorescence microscope imaging. Finally, the 4-(4-nitrobenzyl)pyridine (NBP) colorimetric assay was executed to examine the ability of CBL-based polymeric nanomaterials towards alkylation of DNA.
- |||||||||| Leustatin (cladribine) / J&J, cyclophosphamide intravenous / Generic mfg.
Review, Journal: A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices. (Pubmed Central) - Jan 24, 2020
However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time, hence it became choice of method for the analysis of various drugs. In this review, an overview of reported various bioanalytical methods (HPLC or LC-MS/MS) for the quantification of drugs for the treatment of CLL is given along with applicability of these methods is critically discussed.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Clinical, Journal: Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment. (Pubmed Central) - Jan 5, 2020
This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.
- |||||||||| Leukeran (chlorambucil) / GSK, CEN-209 / Cancer Research Technology, Tirazone (tirapazamine) / Teclison, SRI
Journal: Benzotriazine Di-Oxide Prodrugs for Exploiting Hypoxia and Low Extracellular pH in Tumors. (Pubmed Central) - Dec 19, 2019
Further, the modulation of intracellular reductase activity and competition by the cell-excluded electron acceptor WST-1 suggests that the majority of metabolic reductions of BTO acids occur at the cell surface, compromising the engagement of the resulting free radicals with intracellular targets. Thus, the present study provides support for designing bioreductive prodrugs that exploit pH-dependent partitioning, suggesting, however, that that the approach should be applied to prodrugs with obligate intracellular activation.
- |||||||||| Ukoniq (umbralisib) / TG Therap, Briumvi (ublituximab-xiiy) / TG Therap
Trial primary completion date, Combination therapy: UNITY-CLL: Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Participants With Untreated and Previously Treated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Dec 5, 2019
P3, N=600, Active, not recruiting,
Thus, the present study provides support for designing bioreductive prodrugs that exploit pH-dependent partitioning, suggesting, however, that that the approach should be applied to prodrugs with obligate intracellular activation. Trial primary completion date: Nov 2019 --> Nov 2020
- |||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Imbruvica (ibrutinib) / AbbVie, J&J
Trial completion, Combination therapy: iLLUMINATE : A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment na (clinicaltrials.gov) - Nov 19, 2019
P3, N=229, Completed,
Trial primary completion date: Nov 2019 --> Nov 2020 Active, not recruiting --> Completed
- |||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Calquence (acalabrutinib) / AstraZeneca
Clinical, P3 data, Journal: ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL). (Pubmed Central) - Nov 18, 2019
Wong:Acerta Pharma: Employment. Byrd:Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; BeiGene: Research Funding; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau.
- |||||||||| cyclophosphamide intravenous / Generic Mfg., Rituxan (rituximab) / Roche, Biogen
Journal: The Treatment of Chronic Lymphatic Leukemia. (Pubmed Central) - Nov 8, 2019
Recent progress in the development of novel treatment options gives hope that CLL may soon be a controllable disease. Even at present, chemoimmuno- therapy can achieve a progression-free survival of more than eight years in certain genetically defined subgroups of CLL patients.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen
Cost-Effectiveness of a 12-Month Fixed Duration of Venetoclax in Combination with Obinutuzumab in First-Line Chronic Lymphocytic Leukemia in the United States (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6500;
P3
VenG is projected to be cost-effective vs. ClbG within accepted US cost-effectiveness thresholds. Compared with BR and IBR-based treat-to-progression regimens (IBR, IR, and IG), a 12-month fixed-duration treatment option with VenG seems cost saving and more efficacious based on the CEM.
- |||||||||| A Phase 3 Trial Comparing the Efficacy and Safety of Acalabrutinib in Combination with Venetoclax with or without Obinutuzumab, Compared with Investigator’s Choice of Chemoimmunotherapy in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) without Del(17p) or TP53 Mutation (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6063;
P3
Recently completed phase 3 trials showed acalabrutinib ± obinutuzumab (obi) improved PFS vs chemotherapy in untreated patients (ELEVATE TN: AstraZeneca Press release 06/06/2019), and acalabrutinib improved PFS vs idelalisib or bendamustine + rituximab in relapsed/refractory patients (ASCEND: Ghia et al...In the phase 3 CLL-14 trial in untreated patients with CLL, fixed duration treatment with obi (6 months) + ven (12 months) was more efficacious than obi (6 months) + chlorambucil (12 months), achieving a longer PFS and higher rate of uMRD (Fischer et al...Study design and ACE-CL-311 (NCT03836261) is a 3-arm phase 3, randomized (1:1:1), global, multicenter, open-label trial evaluating the efficacy and safety of acalabrutinib + ven (Arm A) vs acalabrutinib + ven + obi (Arm B) vs CIT (Arm C: fludarabine/cyclophosphamide/rituximab [FCR; only for patients ≤ 65 years of age] or bendamustine/rituximab [BR])...Key exclusion criteria include stroke or intracranial hemorrhage, significant cardiovascular disease (asymptomatic or controlled atrial fibrillation allowed), bleeding disorders, or a requirement for treatment with warfarin or equivalent vitamin K antagonists or a strong cytochrome P450 inhibitor...The study is powered to achieve ~90% power to detect a hazard ratio of 0.65 in PFS comparing Arm A to Arm C, assuming median PFS of 44.7 months in FCR/BR at the 2-sided significance level of 0.05. Patients will be stratified based on age (>65 vs ≤65 years), IGHV mutational status (mutated vs unmutated), Rai stage risk (high [≥3] vs non-high [<3]), and geographic location (North America vs Europe vs Other).
- |||||||||| Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen, bendamustine / SymBio, Mundipharma, Astellas, Generic mfg.
Final Results from the Multicenter, Open-Label, Phase II GIBB Study of Obinutuzumab+Bendamustine in Previously Untreated Patients with Chronic Lymphocytic Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6062;
P2
Complete response and MRD− in peripheral blood were achieved in approximately half of all patients after induction treatment and persisted over time. IgVH mutated status was associated with a longer duration of MRD− and median PFS.
- |||||||||| The Use of CEP (Lomustine, Etoposide and Prednisone), an All-Oral Palliative Chemotherapy Regimen, in Aggressive Lymphomas (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5868;
The median OS in our population is comparable to pooled clinical trial and academic center data from non-transplant eligible patients with R/R DLBCL (Crump et al, Blood, 2017). Some patients even in spite of low performance statuses were able to tolerate many cycles of CEP with a long period of disease control, suggesting it is a reasonable treatment option for frail patients to balance disease control with an acceptable side-effect profile.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Clonal B-Cell Lymphocytosis with Mariginal-Zone Features: Comparison with Overt Splenic Marginal-Zone Lymphomas in 77 Patients from a Monocentric Series (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5750;
Among 4 pts treated, 2 received Rituximab-based regimen, both achieving CR and 2 with Chlorambucil both experiencing progression...Considering the SMZL group, 34 pts underwent systemic treatment (rituximab-based in 32, including R-Bendamustine in 17)...In contrast with previous findings, the WHO 16 CBL cut-off defining MBL (5 x 109/l), together with advanced age, retained prognostic relevance for TTP. Finally, we confirmed for the first time in an independent series of SMZL the highly prognostic impact of Early POD24.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
An Analysis from the WM UK Rory Morrison Registry: Waldenström's Macroglobulinaemia Patient Demographics, Disease Characteristics and Evolving Treatment Choices (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5749;
BTK-inhibitors have become the most commonly used second line therapy, representing 23% of second line therapy after 2010, reflecting the availability of Ibrutinib on the Cancer Drugs Fund from 2017 and the availability of BTKi trials since 2015...OS rates are high and correlate with IPSSWM risk, but a majority of patients had received multiple lines of therapy reflecting the chronically relapsing nature of WM. Treatment practices are clearly evolving, with increasing first line use of DRC and R-Bendamustine, as well as BTK inhibitors for relapsed disease.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Overall Survival, Adverse Events, and Economic Burden in Medicare Patients with Chronic Lymphocytic Leukemia Receiving Cancer-Directed Therapy (Valencia A (W415A), Level 4 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5096;
Over two-thirds of patients survived ≥2 years after start of the first observed therapy during the study period. Incidence for several hematologic and nonhematologic AEs during the common CLL therapies observed in this study appear to be higher than those reported in the noted clinical trials, highlighting potentially greater susceptibility to these AEs and an unmet medical need in Medicare patients with CLL treated in routine practice.
- |||||||||| Trisenox (arsenic trioxide) / Teva, Medsenic, Leukeran (chlorambucil) / GSK
Therapeutic Targeting of RUNX-NFATC2 Axis for Acute Promyelocytic Leukemia and T Cell Immunity (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4564;
Chb-M’ was remarkably more effective against NB4 (IC50 value at nM level) than ATRA and arsenic trioxide...Taken together, we have shown that RUNX transcriptionally upregulated NFATC2, which is essential for APL proliferation and T cell activation . RUNX-NFATC2 axis can be a novel therapeutic target against DR-APL and GVHD.
- |||||||||| rhIL-15 / National Cancer Institute, Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen
Phase 1 Trial of Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocytic Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4244;
Obinutuzumab is a glycoengineered, humanized type 2 anti-CD20 monoclonal antibody thought to engage the immune system by directly activating antibody- dependent, cell-mediated cytotoxicity (ADCC); it is approved for treatment of chronic lymphocytic leukemia in combination with chlorambucil...Preclinical murine lymphoid malignancy models have shown increased efficacy of monoclonal antibodies when administered together with rhIL-15; BL/6 mice inoculated with EL4-CD20 cells (a syngeneic lymphoma line); including significant prolongation of survival with the IL-15/Rituximab combination compared to either drug given as single agent (90% v...Primary objective: determine the safety, toxicity profile, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of civ rhIL-15 administration in combination with obinutuzumab treatment Secondary objectives: 1) evaluate the potential antitumor activity of the combination of rhIL-15 and obinutuzumab by assessing the clinical response rate, minimal residual disease (MRD) status, progression-free survival, and overall survival in patients with relapsed and refractory CLL; 2) define the effects of rhIL-15 on the ADCC mediated by obinutuzumab using ex vivo peripheral blood mononuclear cells (PBMCs); 3) characterize the biological effects of rhIL-15 administered with obinutuzumab on the percentages and absolute numbers of circulating lymphocytes (T and NK cells) and the T- cell subsets (including naïve, central, and effector memory subsets) by flow cytometry Exploratory objectives: identify biomarkers predictive of response to rhIL-15 and obinutuzumab treatment, such as circulating tumor DNA (ctDNA) and baseline cytokine levels Eligibility criteria: 1) age ≥ 18 years; 2) ECOG ≤ 1; 3) Diagnosis of CLL or small lymphocytic lymphoma (SLL) with ≥ 50% of B cells expressing CD20; 4) measurable or evaluable disease that is refractory or relapsed following therapy with a BTK inhibitor OR have relapsed/refractory CLL and are intolerant to BTK inhibitor therapy; patients with del(17p) must also be refractory or relapsed after, or intolerant to, therapy with venetoclax; 5) adequate organ function parameters as defined within the protocol; 6) active disease requiring treatment, as defined within the protocol...One patient has started treatment to date . Enrollment is ongoing.
- |||||||||| Campath (alemtuzumab) / Sanofi, fluconazole / Generic mfg., Rituxan (rituximab) / Roche, Biogen
Fungal Infections in Chronic Lymphocytic Leukemia before and after Treatment (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2994;
In this retrospective analysis of CLL patients, treatment for CLL significantly increased the rate of fungal infections, primarily candida and aspergillus. Further study is needed to understand the effect of modern treatments on fungal infections in CLL.
- |||||||||| metformin / Generic mfg., Rituxan (rituximab) / Roche, Biogen, Imbruvica (ibrutinib) / AbbVie, J&J
Ibrutinib Maintenance after Chemoimmunotherapy Is Feasible and Results in Excellent Progression-Free and Overall Survival in Patients with Detectable MRD after Chemoimmunotherapy (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2606;
Twenty-nine patients (73%) had been treated with fludarabine and cyclophosphamide (FC) ± rituximab, 10 (25%) with chlorambucil ± rituximab, and one (2%) with bendamustine + rituximab...Adverse events of any grade that occurred during maintenance with ibrutinib included diarrhea (23%), nausea (10%), and fatigue (8%), but only 2 patients had grade 3 diarrhea, associated with the concomitant use of metformin that resolved after discontinuation...Conclusions Maintenance with ibrutinib for CLL patients achieving CR or PR after chemoimmunotherapy resulted in excellent PFS and OS, and sustained improvement in hematologic variables irrespectively of achieving undetectable MRD. Efficacy of this regimen compares well to other frontline chemo-free treatments offered to patients with CLL in the United States and Europe.
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