Delving into the Latest Updates on Bendamustine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BENDA, Bendam, Bendamus

+ [36]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [5]

Active Indication

Diffuse Large B-Cell LymphomaB-Cell LymphomaLymphoid Leukemia+ [28]

Inactive Indication

acute leukemiaAcute myeloid leukaemia with 11q23 abnormalityAcute Myeloid Leukemia+ [49]

Originator Organization

SymBio Pharmaceuticals Ltd.

Active Organization

Accord Healthcare, Inc.

National Cancer Institute

Jiangsu Aosaikang Pharmaceutical Co. Ltd.

+ [15]

Inactive Organization

Caen University HospitalWyeth AB

TG Therapeutics, Inc.

+ [28]

Drug Highest PhaseApproved

First Approval Date

US (20 Mar 2008),

Chronic Lymphocytic Leukemia

RegulationOrphan Drug (US), Priority Review (CN), Orphan Drug (JP)

Login to view First Approval Timeline

Structure

Molecular FormulaC16H22Cl3N3O2

InChIKeyZHSKUOZOLHMKEA-UHFFFAOYSA-N

CAS Registry3543-75-7

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

Start Date01 Jul 2024

Sponsor / Collaborator

Fred Hutchinson Cancer Center

[+1]

NCT06363994 / Not yet recruitingPhase 3

A Randomized, Double-Blind, Multicenter, Placebo-Controlled Phase 3 Study of Orelabrutinib in Combination With Rituximab and Bendamustine (BR) vs. BR in Subjects With Treatment-Naїve Mantle Cell Lymphoma

Compare the efficacy and safety of Orelabrutinib plus bendamustine+ rituximab versus bendamustine + rituximab in previously untreated patients with mantle cell lymphoma (MCL)

Start Date25 May 2024

Sponsor / Collaborator

Beijing InnoCare Pharma Tech Co., Ltd.

100 Clinical Results associated with Bendamustine Hydrochloride

Login to view more data

100 Translational Medicine associated with Bendamustine Hydrochloride

Login to view more data

100 Patents (Medical) associated with Bendamustine Hydrochloride

Login to view more data

2,780

Literatures (Medical) associated with Bendamustine Hydrochloride

01 Mar 2024·Food chemistry: X

Improvement of oxidized myofibrillar protein gel properties by black rice extract

Article

Author: Wang, Huali ; Chen, Guijie ; Kay, Matthew ; Zhang, Daojiu ; Li, Xiang

In order to investigate the effects of black rice extract (BE) on the composition of oxidized myofibrillar protein (MP) gel, different concentrations of BE (0, 10, 20, 50 mg g^-1) were analyzed experimentally. Results revealed that the addition of small doses of BE significantly inhibited the formation of carbonyl groups in oxidized MP, and improved surface hydrophobicity and gel water holding capacity. Additionally, 10 and 20 mg g^-1 BE increased the ordered structure of oxidized MP. Furthermore, dynamic rheometer results showed a significant increase in the storage modulus (G') of oxidized MP with 10 and 20 mg g^-1 BE during heating. Scanning Electron Microscopy (SEM) showed that MP formed a denser network structure with addition of 10 and 20 mg g^-1 BE. Low-Field Nuclear Magnetic Resonance (LF-NMR) and magnetic resonance imaging (MRI) showed that there is a significant increase in immobile water in MP gel and a decrease in free water within the 20 mg g^-1 BE group. In conclusion, 20 mg g^-1 supplemented BE significantly improved the structure order and hardness of oxidized MP gel, increased its structure density and water holding capacity, and it provides a theoretical basis for the application of antioxidants in meat products.

01 Mar 2024·Journal of hazardous materials

Remediation of biochar-supported effective microorganisms and microplastics on multiple forms of heavy metals in eutrophic lake

Article

Author: Gong, Jilai ; Tang, Siqun ; Cao, Weicheng ; Song, Biao ; Li, Juan

In mineral-rich areas, eutrophic lakes are at risk of HMs pollution. However, few papers focused on the repair of HMs in eutrophic environment. Our study analyzed multiple forms of HMs, pore structure and microbial responses in the water-sediment system of eutrophic lake treated with biochar, Effective Microorganisms (EMs) or/and microplastics (MPs). As biochar provided an ideal carrier for EMs, the remediation of biochar-supported EMs (BE) achieved the greatest repairment that improved the bacterial indexes and greatly decreased the most HMs in various forms across the water-sediment system, and it also reduced metal mobility, bioavailability and ecological risk. The addition of aged MPs (MP) stimulated the microbial activity and significantly reduced the HMs levels in different forms due to the adsorption of biofilms/EPS adhered on MPs, but it increased metals mobility and ecological risks. The strong adsorption and high mobility of aged MPs would increase enrichment of HMs and cause serious ecological hazards. The incorporation of BE and MP (MBE) also greatly reduced the HMs in full forms, which was primarily ascribed to the adsorption of superfluous biofilms/EPS, but it distinctly depressed the microbial activity. The single addition of biochar and EMs resulted in the inability of HMs to be adsorbed due to the preferentially adsorption of dissolved nutrients and the absence of effective carrier, respectively. In the remediation cases, the remarkable removal of HMs was principally accomplished by the adsorption of HMs with molecular weight below 100 kDa, especially 3 kDa ∼100 kDa, which had higher specific surfaces and abundant active matters, resulting in higher adsorption onto biofilms/EPS.

13 Feb 2024·Blood advances

Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines

Article

Author: Schuster, Stephen J ; Chong, Eise A ; Yelton, Rebecca ; Napier, Ellen ; White, Griffin ; Shestov, Alexander A ; Porazzi, Patrizia ; Nasta, Sunita D ; Pajarillo, Raymone ; Weber, Elizabeth ; O'Connor, Roderick ; Patel, Vrutti ; Garfall, Alfred L ; Ghilardi, Guido ; Svoboda, Jakub ; Ballard, Hatcher J ; Barta, Stefan K ; Gerson, James N ; Landsburg, Daniel J ; Chen, Linhui ; Ruella, Marco ; Porter, David L ; Fraietta, Joseph A ; Milone, Michael C ; Carter, Jordan ; Gabrielli, Giulia ; Paruzzo, Luca ; Chong, Emeline R ; Cohen, Ivan J

Abstract:

Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.

169

News (Medical) associated with Bendamustine Hydrochloride

27 Jun 2024

·www.globenewswire.com

Release Therapeutics Announces New CEO to Drive Best-in-Class CNS Innovation

The appointment aligns with the company’s recent strategic pivot towards treating genetic disorders of the CNS without gene therapyGENEVA, June 27, 2024 (GLOBE NEWSWIRE) -- Release Therapeutics (‘Release Tx’ or ‘the Company’), a privately-held, Swiss BioMedTech company, announced today the appointment of Thomas Mehrling, MD, PhD, as CEO. The appointment follows the recent strategic pivot of Release Tx (formerly, ‘MaxiVax’) towards treating genetic disorders of the central nervous system (CNS) with a best-in-class cell macroencapsulation technology as an alternative to gene therapy.1 With over 25 years’ experience in multinational pharma companies, including Takeda, Mundipharma International and Hoffmann-La Roche, Dr. Mehrling is an expert in developing novel oncology compounds from bench to bedside. During his tenure at MundiPharma International (2003–2013), he oversaw the clinical development, registration and launch of two major products in Europe, Depocyte® and Levact® (Ribomustin® and Treanda®). Dr. Mehrling received his PhD in Pharmacology and MD from the University of Frankfurt, where he previously spent 13 years working on research projects in cardiology and oncology. Release Tx is developing a proprietary technology capable of delivering highly potent therapeutic proteins beyond the blood-brain barrier (BBB) for the long-term treatment of CNS disorders. Consisting of an implantable macroencapsulation device and a human myoblast cell line that can be genetically modified to produce diverse proteins, this technology is the first of its kind to be designed for cell macroencapsulation in humans.2 The lead programme of Release Tx focuses on treating Metachromatic Leukodystrophy (MLD), a rare genetic CNS disorder typically affecting young children. Release Tx’s Chairman, Ksenija Pavletic, said, “We’re thrilled to have Dr. Mehrling on board to lead Release Therapeutics on its new mission. The remarkable progress we’ve made with our technology now offers significant advantages over gene therapy for the treatment of CNS diseases, bringing hope to patients and their families around the world.” Thomas Mehrling, MD, PhD, said ‘Release Therapeutics’ technology is a game-changer in getting therapeutic proteins where they are needed most. I am looking forward to driving the company towards this goal.’ References (1) https://www.release-tx.com/post/treating-genetic-disorders-of-the-cns-without-gene-therapy-or-what-we-ve-been-up-to-here-at-release(2) https://www.release-tx.com/post/release-therapeutics-publishes-cutting-edge-research-in-cell-press About Release Therapeutics Headquartered in Geneva, Switzerland, Release Therapeutics is a privately-held, BioMedTech company developing the first cell macroencapsulation technology designed to deliver potent therapeutic proteins beyond the human blood-brain barrier. The Company’s proprietary technology integrates an implantable macroencapsulation device with an immortalised myoblast cell line capable of producing a broad range of proteins for long-term delivery to the CNS. Innovating at the nexus of biotech and MedTech, Release Therapeutics is on a mission to treat genetic diseases of the CNS without gene therapy. The company’s lead programme is in preclinical development for the treatment of Metachromatic Leukodystrophy (MLD), a rare genetic disorder that leads to progressive loss of myelin and typically affects young children. For more information, please visit our website: https://www.release-tx.com/ Contacts Release Therapeutics SAcontact@release-tx.com Manage Mind Greece (for Release Therapeutics)Jessica KourniaktisPhone: (+30)6932254679Email: jkourniakti@managemind.ch

Executive ChangeGene Therapy

18 Jun 2024

·www.biospace.com

AstraZeneca’s Truqap Flops in Phase III Triple-Negative Breast Cancer Trial

Pictured: AstraZeneca's manufacturing facility in Sweden/iStock, Fotonen AstraZeneca on Tuesday announced that its AKT inhibitor Truqap (capivasertib), when used in combination with paclitaxel, failed to meet its primary efficacy endpoint in the Phase III CAPItello-290 study in patients with metastatic triple-negative breast cancer. The pharma did not provide specific data in its announcement, only revealing that the Truqap combo failed to significantly improve overall survival in the total study population or in the subgroup of patients with specific mutations in the PIK3CA, AKT1 or PTEN genes. The study compared the Truqap regimen against placebo plus paclitaxel. Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, in a statement said that the pharma is “disappointed” by Tuesday’s readout. Nevertheless, Galbraith said “these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the Truqap clinical development program.” In patients with triple-negative breast cancer (TNBC), tumor cells lack the three most commonly over-expressed receptors in breast cancers—estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2—making them more difficult to target and treat. TNBCs are also typically more aggressive and tend to progress more rapidly. Approximately 35% of TNBC cases show alterations in the PIK3CA, AKT1 and PTEN proteins, according to AstraZeneca. Truqap, a first-in-class and ATP-competitive blocker of AKT, is designed to address an underlying disease pathway in TNBC by blocking all AKT isoforms and disrupting their downstream cascades that would otherwise result in uncontrolled cell proliferation, invasion and metastasis. The FDA approved Truqap in November 2023 for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer, when used in combination with AstraZeneca’s endocrine therapy Faslodex (fulvestrant). The pharma has been trying to expand Truqap’s patient pool by testing it in other types of breast cancer and in other settings of care. CAPItello-290 is part of this push, alongside the Phase III CAPItello-292 study, which is testing the AKT inhibitor with Faslodex and palbociclib as a first-line triplet regimen in patients with locally advanced, inoperable or metastatic HR-positive or HER2-negative breast cancer. AstraZeneca is also assessing Truqap in prostate cancer, for which it is running the CAPItello-280 and CAPItello-281 trials. Tuesday’s Phase III flop breaks AstraZeneca’s recent winning streak in cancer. On Monday, the pharma’s blockbuster drug Imfinzi (durvalumab) won the FDA’s approval for primary advanced or recurrent mismatch repair-deficient endometrial cancer. A day before, AstraZeneca reported that its BTK inhibitor Calquence (acalabrutinib) aced the Phase III ECHO trial, demonstrating significant and meaningful survival benefits when used with bendamustine and rituximab to treat mantle cell lymphoma. Earlier this month, AstraZeneca also recorded Phase III wins for Imfinzi in small cell lung cancer and for the EGFR inhibitor Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Drug ApprovalClinical Result

18 Jun 2024

·pmlive.com

AstraZeneca’s Calquence shows survival benefit in phase 3 mantle cell lymphoma study

AstraZeneca’s (AZ) Bruton’s tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) has been shown to improve progression-free survival (PFS) in patients with previously untreated mantle cell lymphoma (MCL), according to late-stage results presented by the company. The phase 3 ECHO trial has been evaluating the drug plus standard-of-care chemoimmunotherapy, bendamustine and rituximab, compared to chemoimmunotherapy alone in adults aged over 65 years with previously untreated MCL. The results shared at this year’s European Hematology Association Hybrid Congress showed that the Calquence combination reduced the risk of disease progression or death by 27% compared to chemoimmunotherapy. Median PFS was 66.4 months for patients treated with the Calquence combination versus 49.6 months for those receiving chemoimmunotherapy. A trend was also observed in favour of the combination for the secondary endpoint of overall survival (OS), making Calquence the first BTK inhibitor to demonstrate a favourable OS trend versus standard-of-care chemoimmunotherapy in this setting. This data was not mature at the time of the analysis and the trial will continue to further assess OS, AZ said. The company added that ECHO enrolled during the COVID-19 pandemic and a pre-specified analysis that censored COVID-19-related deaths demonstrated a further improvement in PFS, with the Calquence combination reducing the risk of disease progression or death by 36%. Susan Galbraith, executive vice president, oncology research and development, AZ, said: “The ECHO trial data demonstrates important progress in improving outcomes for patients with MCL… We therefore believe Calquence plus chemoimmunotherapy will be an important new option for patients living with this disease.” Estimated to affect more than 27,500 people globally, MCL is a rare and typically aggressive form of non-Hodgkin lymphoma that is often diagnosed as a late-stage disease. Calquence is already approved in the US and several other countries to treat adults with MCL who have received at least one prior therapy, and also holds authorisations to treat certain patients with chronic lymphocytic leukaemia and small lymphocytic lymphoma. ECHO principal investigator, Michael Wang, MD Anderson Cancer Center, said: “The improved PFS seen in patients treated with the Calquence combination compared to chemoimmunotherapy demonstrates its potential to change the standard of care as the only BTK inhibitor in this first-line setting.”

Clinical ResultImmunotherapyPhase 3Drug Approval

100 Deals associated with Bendamustine Hydrochloride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D07085	Bendamustine Hydrochloride	L01AA09	DB06769

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	JP	SymBio Pharmaceuticals Ltd.	28 Apr 2021
B-Cell Lymphoma	CN	Cephalon, Inc.	17 Dec 2018
B-Cell Lymphoma	CN	Roche Holding AG	17 Dec 2018
Lymphoid Leukemia	JP	SymBio Pharmaceuticals Ltd.	26 Aug 2016
Indolent B-Cell Non-Hodgkin Lymphoma	US	Eagle Pharmaceuticals, Inc.	07 Dec 2015
Mantle-Cell Lymphoma	JP	SymBio Pharmaceuticals Ltd.	27 Oct 2010
Chronic Lymphocytic Leukemia	US	Cephalon, Inc.	20 Mar 2008

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Follicular Lymphoma	Phase 3	US	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	AU	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	IL	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	IT	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	PL	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	SK	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	KR	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	ES	TG Therapeutics, Inc.	25 May 2016
Follicular Lymphoma	Phase 3	GB	TG Therapeutics, Inc.	25 May 2016
Marginal Zone B-Cell Lymphoma	Phase 3	US	TG Therapeutics, Inc.	25 May 2016

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


MAINTAIN (ASCO2024)	Not Applicable	Mantle-Cell Lymphoma Maintenance	796	Rituximab maintenance	eezfpwumhe(wmuikqadoi) = fzypczedhl cygfhkkiyk (qrfbbiwtao ) View more	Positive	24 May 2024
MAINTAIN (ASCO2024)	Not Applicable	Mantle-Cell Lymphoma Maintenance	796	No rituximab maintenance	eezfpwumhe(wmuikqadoi) = imrapwxmla cygfhkkiyk (qrfbbiwtao ) View more	Positive	24 May 2024
NCT02467946 (HALO, EHA2024) Manual	Phase 1/2	Hodgkin's Lymphoma First line	59	BENDAMUSTINE+ADCETRIS	wpyhdjofdp(jtkuvhfudr) = for co-morbidity, showed that (1) 38/54 (70%) had ≥ 5comorbidities, 15 of them (27%) with a score 3 (organ damage). qpgprteaqn (zrtnttkasg ) View more	Positive	14 May 2024
MAINTAIN (EHA2024)	Not Applicable	Mantle-Cell Lymphoma Maintenance	796	Rituximab maintenance	umejlinytn(isbufjffzk) = cmwdcegewx clrjdrakdf (grqwkjgcjx ) View more	Positive	14 May 2024
MAINTAIN (EHA2024)	Not Applicable	Mantle-Cell Lymphoma Maintenance	796	No Rituximab maintenance	umejlinytn(isbufjffzk) = qdobjgqckm clrjdrakdf (grqwkjgcjx ) View more	Positive	14 May 2024
REAL-LIFE STUDY OF POLATUZUMAB VEDOTIN, BENDAMUSTINE AND RITUXIMAB (EHA2024)	Not Applicable	Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma	-	Polatuzumab vedotin, bendamustine and rituximab (Pola-BR)	gnycltgvwn(lxfgehiljc) = vvienpdtbh rbbzffeapv (pngwhvtyxy ) View more	Negative	14 May 2024
NCT04510636 (KEsTREL-01, EHA2024)	Phase 2	Hodgkin's Lymphoma	37	Pembrolizumab 200 mg IV + Bendamustine 90 mg/m2 IV	mlurfgyyyt(lsvfpryfjp) = sufdacyksg qxqcsswljj (vtogsblpta ) View more	Positive	14 May 2024
EHA2024	Not Applicable	Lymphoma First line	219	Bendamustine plus rituximab	yzceazwyit(fwtvcgeqek) = 2 cases of CMV infection occurred in patients who had not received maintenance therapy mxlkxtmsox (ssnynkqero ) View more	-	14 May 2024
EHA2024	Not Applicable	Refractory Hodgkin Lymphoma	19	Brentuximab Vedotin + Bendamustine	lutxlwmvkb(yafxiunlep) = 23.1% of cycles (14.5% of grade 4) aqsmblmftx (bxglwzlvhh ) View more	Positive	14 May 2024
NCT01059786 (CTgov)	Phase 2	Hairy Cell Leukemia	69	Corticosteroids+Bronchodilators+Bendamustine+Acetaminophen+Epinephrine+Intravenous (IV) Saline+Pentostatin+Diphenhydramine+Rituximab	vyvvfrrgtt(uwlfikuvxy) = yngtzsupgj roxxnibfmi (ltdgrazpnp, kjafeoelic - yknzvcydbb) View more	-	01 May 2024
NCT03834688 (CTgov)	Phase 2	Mantle-Cell Lymphoma	33	Bendamustine+Venetoclax+Rituximab	yqswwzngpl(xsgfxntdef) = yxutwjkkdv wpdyyiotoy (pqtkkykzze, oqrmikgkyu - kvyswcomuj) View more	-	23 Jan 2024
ASH2023	Not Applicable	Mantle-Cell Lymphoma	33	Bendamustine, Rituximab, and Venetoclax (BR-VEN)	iiriebljme(cpversoogq) = There were 4 (12%) instances of COVID-19/COVID-19 pneumonia considered treatment related ifyclreept (ztcvrxgyvs )	-	11 Dec 2023