We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

4 days ago

Journal

LAG3 (Lymphocyte Activating 3) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • ITGAM (Integrin, alpha M) • CD7 (CD7 Molecule)

daunorubicin • valrubicin

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation. (PubMed, BMC Complement Med Ther)

CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin® alone or in combination with GC for the management of chronic ITP.

4 days ago

PK/PD data • Journal

CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • FOXP3 (Forkhead Box P3) • IL17A (Interleukin 17A)

ABCB1 expression

daunorubicin

(2,6-Dimethylphenyl)arsonic Acid Induces Apoptosis through the Mitochondrial Pathway, Downregulates XIAP, and Overcomes Multidrug Resistance to Cytostatic Drugs in Leukemia and Lymphoma Cells In Vitro. (PubMed, Int J Mol Sci)

Further experiments showed that As2 overcomes multidrug resistance and sensitizes drug-resistant leukemia and lymphoma cell lines to treatments with the common cytostatic drugs vincristine, daunorubicin, and cytarabine at low micromolar concentrations. Downregulation of XIAP (x-linked inhibitor of apoptosis protein) and apoptosis induction independent of Bcl-2 (B-cell lymphoma 2) and caspase-3 expression levels suggest the activation of additional apoptosis-promoting mechanisms. Due to the selective apoptosis induction, the synergistic effects with common anti-cancer drugs, and the ability to overcome multidrug resistance in vitro, As2 represents a promising candidate for further preclinical investigations with respect to refractory malignancies.

4 days ago

Preclinical • Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • FADD (Fas associated via death domain) • CASP3 (Caspase 3) • CASP9 (Caspase 9) • XIAP (X-Linked Inhibitor Of Apoptosis)

cytarabine • vincristine • daunorubicin

UKALL14: Standard Chemotherapy With or Without Nelarabine or Rituximab in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P3, N=1033, Active, not recruiting, University College, London | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

6 days ago

Trial completion date • Trial primary completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC translocation • Chr t(4;11)(q21;q23)

Rituxan (rituximab) • imatinib • cytarabine • cyclophosphamide • etoposide IV • vincristine • daunorubicin • melphalan • Oncaspar liquid (pegaspargase) • fludarabine IV • nelarabine • mercaptopurine • Kepivance (palifermin)

Optimum Induction Therapy of Low-risk APL (clinicaltrials.gov)

P=N/A, N=74, Recruiting, Peking University People's Hospital | Trial primary completion date: Feb 2024 --> Dec 2024

6 days ago

Trial primary completion date

RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)

etoposide IV • daunorubicin

Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) (clinicaltrials.gov)

P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=154 --> 0 | Not yet recruiting --> Withdrawn

8 days ago

Enrollment change • Trial withdrawal

Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • navitoclax (ABT 263) • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

10d

Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=40, Completed, Wake Forest University Health Sciences | Unknown status --> Completed | Phase classification: P2 --> P1

10 days ago

Trial completion • Phase classification

cytarabine • daunorubicin • Starasid (cytarabine ocfosfate)

10d

A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT) (clinicaltrials.gov)

P3, N=1656, Not yet recruiting, Children's Oncology Group

10 days ago

New P3 trial

carboplatin • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • irinotecan • vincristine • daunorubicin • dactinomycin

13d

Pharmacological p38 MAPK inhibitor SB203580 enhances AML stem cell line KG1a chemosensitivity to daunorubicin by promoting late apoptosis, cell growth arrest in S-phase, and miR-328-3p upregulation. (PubMed, Saudi Pharm J)

Remarkably, the enhanced KG1a cell sensitivity to DNR after SB203580 pretreatment was associated with an increased upregulation of miR-328-3p and slight downregulation of miR-26b-5p, compared to DNR effect. Altogether, these findings could contribute to the development of a new therapeutic strategy by targeting the p38 MAPK pathway to improve treatment outcomes in patients with refractory or relapsed AML.

13 days ago

Preclinical • Journal • IO biomarker

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3) • CASP9 (Caspase 9) • CASP7 (Caspase 7) • MIR328 (MicroRNA 328) • CCNB1 (Cyclin B1)

BCL2 expression • TP53 expression

daunorubicin

14d

Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma (clinicaltrials.gov)

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

14 days ago

Trial completion date • Trial primary completion date

Opdivo (nivolumab) • doxorubicin hydrochloride • Adcetris (brentuximab vedotin) • dacarbazine • daunorubicin • bleomycin • vinblastine

16d

Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov)

P2, N=145, Not yet recruiting, St. Jude Children's Research Hospital

16 days ago

New P2 trial

Venclexta (venetoclax) • dasatinib • cytarabine • bortezomib • cyclophosphamide • vincristine • daunorubicin • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine

16d

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma (clinicaltrials.gov)

P3, N=478, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

16 days ago

Enrollment open • Surgery

ALK (Anaplastic lymphoma kinase) • TERT (Telomerase Reverse Transcriptase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

cisplatin • carboplatin • temozolomide • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • irinotecan • vincristine • daunorubicin • topotecan • melphalan • thiotepa • Qarziba (dinutuximab beta) • Unituxin (dinutuximab) • dexrazoxane

16d

Selinexor With Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients (clinicaltrials.gov)

P2, N=100, Recruiting, Wake Forest University Health Sciences | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

16 days ago

Trial completion date • Trial primary completion date • Combination therapy

cytarabine • Xpovio (selinexor) • daunorubicin • Starasid (cytarabine ocfosfate)

17d

Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL (clinicaltrials.gov)

P3, N=81, Recruiting, First Affiliated Hospital of Zhejiang University | Not yet recruiting --> Recruiting

17 days ago

Enrollment open

Venclexta (venetoclax) • cytarabine • cyclophosphamide • daunorubicin • Synribo (omacetaxine mepesuccinate) • vindesine

21d

Polatuzumab Vedotin and Combination Chemotherapy for the Treatment of Untreated Aggressive Large B-cell Lymphoma (clinicaltrials.gov)

P1, N=50, Suspended, University of Washington | Recruiting --> Suspended

21 days ago

Trial suspension

ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

BCL6 translocation

Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • prednisone • daunorubicin • Polivy (polatuzumab vedotin-piiq) • Neupogen (filgrastim)

21d

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov)

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

21 days ago

Trial initiation date • Combination therapy

MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1)

BCL2 expression

Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • Rylaze (recombinant Erwinia asparaginase) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

21d

Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) (clinicaltrials.gov)

P2, N=154, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Aug 2024

21 days ago

Trial initiation date

21d

Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis. (PubMed, BMC Cancer)

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.

21 days ago

Journal

MCL1 (Myeloid cell leukemia 1)

cytarabine • daunorubicin • Synribo (omacetaxine mepesuccinate)

21d

A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)

P3, N=680, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

21 days ago

Trial initiation date

ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)

CD19 expression

TruSight RNA Pan-Cancer Panel

dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)

28d

Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

28 days ago

Trial completion date • Trial primary completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD20 (Membrane Spanning 4-Domains A1) • CD22 (CD22 Molecule) • ITGB1 (Integrin Subunit Beta 1)

CD20 positive • CD22 positive

Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Besponsa (inotuzumab ozogamicin) • vincristine • daunorubicin • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine

29d

Inhibition of NRF2 signaling overcomes acquired resistance to arsenic trioxide in FLT3-mutated Acute Myeloid Leukemia. (PubMed, Ann Hematol)

We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples. We examined the effects of molecular/pharmacological suppression of NRF2 on acquired ATO resistance in the FLT3-ITD mutant AML cell line (MV4-11-ATO-R). Digoxin decreased leukemic burden and prolonged survival in MV4-11 ATO-R xenograft mice. We establish that altering NRF2 expression may reverse acquired ATO resistance in FLT3-ITD AML.

29 days ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • GLI2 (GLI Family Zinc Finger 2)

FLT3-ITD mutation • FLT3 mutation

daunorubicin • arsenic trioxide

29d

NCI-2018-03732: Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma (clinicaltrials.gov)

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Sep 2024

29 days ago

Trial completion date

MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL6 (Interleukin 6) • CXCL9 (Chemokine (C-X-C motif) ligand 9)

MYCN amplification • IL6 expression

cisplatin • carboplatin • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • daunorubicin • topotecan • melphalan • thiotepa • Qarziba (dinutuximab beta) • Unituxin (dinutuximab) • Leukine (sargramostim) • dexrazoxane

29d

Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P1, N=130, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1

29 days ago

Enrollment closed • Phase classification • Combination therapy

cytarabine • cyclophosphamide • vincristine • daunorubicin • carfilzomib • mitoxantrone • Oncaspar liquid (pegaspargase) • mercaptopurine • dexamethasone injection

ENHANCE-2: Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated (clinicaltrials.gov)

P3, N=258, Terminated, Gilead Sciences | Active, not recruiting --> Terminated; Study discontinued due to futility.

1 month ago

Trial termination • Combination therapy

TP53 (Tumor protein P53)

TP53 mutation

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • magrolimab (ONO-7913)

A Phase III Study Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL (clinicaltrials.gov)

P3, N=81, Not yet recruiting, First Affiliated Hospital of Zhejiang University

1 month ago

New P3 trial

Venclexta (venetoclax) • cytarabine • cyclophosphamide • daunorubicin • Synribo (omacetaxine mepesuccinate) • vindesine

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

1 month ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)

VA vs DA for Newly Diagnosed Hig-risk AML (clinicaltrials.gov)

P2/3, N=116, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Jul 2027 --> Oct 2027 | Initiation date: Jul 2023 --> Apr 2024 | Trial primary completion date: Jul 2025 --> Oct 2025

1 month ago

Trial completion date • Trial initiation date • Trial primary completion date

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin

AALL0434: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma (clinicaltrials.gov)

P3, N=1895, Active, not recruiting, National Cancer Institute (NCI)

1 month ago

Trial completion date

CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD22 (CD22 Molecule) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • MPO (Myeloperoxidase)

CD22 expression

cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Kidrolase (L-asparaginase) • Leunase (L-asparaginase) • Spectrila (asparaginase Escherichia coli) • Starasid (cytarabine ocfosfate) • dexamethasone injection

RCT on the MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) (clinicaltrials.gov)

P3, N=154, Recruiting, Zhongnan Hospital

1 month ago

New P3 trial

azacitidine • daunorubicin • Duoenda (mitoxantrone liposomal)

2ms

Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity. (PubMed, J Cancer Res Clin Oncol)

DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

2 months ago

Journal

BCL2 (B-cell CLL/lymphoma 2) • CCN1 (Cellular Communication Network Factor 1)

daunorubicin

2ms

Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells. (PubMed, Mol Biol Rep)

Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression.

2 months ago

Journal • IO biomarker

PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

ABCB1 overexpression • TP53 expression

daunorubicin

2ms

Dosing of 7 + 3 induction chemotherapy in a patient with acute myeloid leukemia (AML) and morbid obesity. (PubMed, J Oncol Pharm Pract)

This case suggests that dose capping of anthracyclines in the treatment of newly diagnosed AML may be an effective and safe treatment alternative in those with extreme BMI elevations beyond what has been studied in the literature. Given the increasing incidence of morbid obesity, further studies are needed to confirm appropriate dosing of anthracycline-based regimens at upper BMI extremes (>60 kg/m2).

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

IDH2 mutation • NPM1 mutation

cytarabine • daunorubicin

2ms

Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling. (PubMed, Cell Death Discov)

Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

2 months ago

Journal

CD34 (CD34 molecule)

cytarabine • azacitidine • daunorubicin

2ms

P2, N=171, Not yet recruiting, National Cancer Institute (NCI)

2 months ago

New P2 trial • Combination therapy

MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1)

BCL2 expression

2ms

Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis. (PubMed, Molecules)

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity.

2 months ago

Journal

BCL2 (B-cell CLL/lymphoma 2) • CASP9 (Caspase 9)

doxorubicin hydrochloride • daunorubicin

2ms

Phase I Trial of Revumenib in Combination With 7+3+Midostaurin (clinicaltrials.gov)

P1, N=22, Not yet recruiting, Maximilian Stahl, MD

2 months ago

New P1 trial • Combination therapy

Rydapt (midostaurin) • daunorubicin • revumenib (SNDX-5613)

2ms

Metabolic engineering of Streptomyces peucetius for biosynthesis of N,N-dimethylated anthracyclines. (PubMed, Front Bioeng Biotechnol)

To achieve this, we introduced genes from the aclarubicin biosynthetic pathway encoding the sugar N-methyltransferases AclP and AknX2. DoxA is the key enzyme that determines the efficiency of the biosynthesis of N,N-dimethylated anthracyclines, and engineering of this enzyme will be a major step forwards towards the efficient production of more N,N-dimethylated anthracyclines, including N,N-dimethyldoxorubicin. This study provides valuable insights into the biosynthesis of clinically relevant daunorubicin derivatives, highlighting the importance of combinatorial biosynthesis.

2 months ago

Journal

AEBP1 (AE Binding Protein 1)

doxorubicin hydrochloride • daunorubicin • aclarubicin

2ms

Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)

P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027

2 months ago

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

2ms

Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma (clinicaltrials.gov)

P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

2 months ago

Trial completion date • Trial primary completion date • Metastases

everolimus • temozolomide • doxorubicin hydrochloride • Votrient (pazopanib) • cyclophosphamide • ifosfamide • irinotecan • Torisel (temsirolimus) • vincristine • daunorubicin • ganitumab (AMG 479)

2ms

P3; Initiation date: Jan 2024 --> Apr 2024

2 months ago

Trial initiation date

CD19 expression

TruSight RNA Pan-Cancer Panel

2ms

Effect of venetoclax plus chemotherapy on treatment-naive acute myeloid leukemia patients with moderate to poor cytogenetic profiles and the combination's influence on the expression of proteins of the anti-apoptoic family (PubMed, Zhonghua Zhong Liu Za Zhi)

The chemotherapy cohort received 2 cycles of induction chemotherapy (idarbicin or daunorubicin plus cytarabine), followed by 6 cycles of consolidation chemotherapy (cytarabine), while the treatment for the VEN + chemotherapy cohort consisted of the same chemotherapy as above plus oral VEN. VEN combined with intensive chemotherapy have yielded high ORR and survival advantages for de novo AML patients with poor cytogenetics profiles. The high-expression of MCL-1 may drive resistance to VEN.

2 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1)

BCL2 expression • MCL1 expression

Venclexta (venetoclax) • cytarabine • daunorubicin

2ms

Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)

P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual

2 months ago

Trial termination

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • sunitinib • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical