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DRUG:

methotrexate IV

Associations
Company:
Generic mfg.
Drug class:
THF dehydrogenase inhibitor, Dihydrofolic acid reductase inhibitor
Associations
14d
Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.
Retrospective data • Journal
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HER-2 (Human epidermal growth factor receptor 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2) • TBL1XR1 (TBL1X Receptor 1)
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HER-2 mutation • PIM1 mutation
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methotrexate IV
18d
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis (clinicaltrials.gov)
P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Oct 2024 --> Mar 2025
Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 positive • HER-2 negative • ER negative • ER positive + PGR positive • PGR negative • HER-2 negative + AR positive + ER positive • HER-2 negative + PGR positive
|
methotrexate IV
19d
Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition. (PubMed, Int J Mol Sci)
A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin...CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • PTCH1 (Patched 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • GLI1 (GLI Family Zinc Finger 1) • MMP2 (Matrix metallopeptidase 2) • BAX (BCL2-associated X protein) • MMP9 (Matrix metallopeptidase 9) • GLI2 (GLI Family Zinc Finger 2)
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GLI2 overexpression
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cisplatin • doxorubicin hydrochloride • methotrexate • methotrexate IV
28d
New P2 trial
|
Brukinsa (zanubrutinib) • thiotepa • methotrexate IV
2ms
Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype. (PubMed, Neuro Oncol)
This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.
Journal
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TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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TP53 mutation • MYCN amplification
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carboplatin • cyclophosphamide • etoposide IV • methotrexate • thiotepa • methotrexate IV
2ms
Simultaneous Determination of Methotrexate Concentrations in Human Plasma and Cerebrospinal Fluid Using Two-Dimensional Liquid Chromatography: Applications in Primary Central Nervous System Lymphoma. (PubMed, World J Oncol)
The developed method was useful for therapeutic drug monitoring of MTX and suitable for assessing the risks and benefits of chemotherapy in patients with primary central nervous system lymphoma. Intravenous mannitol did not increase MTX concentration in the CSF of patients.
Journal
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MMP7 (Matrix metallopeptidase 7)
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methotrexate • methotrexate IV
2ms
Isolated Primary Central Nervous System Lymphoma of the Optic Nerve: A Case Report and Review of the Literature. (PubMed, Neurologist)
This is the first reported case of isolated optic nerve involvement with a durable response to chemotherapy. This case emphasizes the importance of considering malignancy and maintaining a low threshold for optic nerve biopsy in patients with atypical cases of severe steroid-refractory vision loss with enhancement or enlargement of the optic nerve on MRI. Standard chemotherapy regimens for PCNSL can potentially achieve a curative response in these patients.
Review • Journal
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MVP (Major Vault Protein)
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Rituxan (rituximab) • cytarabine • methotrexate • vincristine • prednisone • Matulane (procarbazine hydrochloride) • methotrexate IV
2ms
Trial completion date
|
Gilotrif (afatinib) • methotrexate IV
2ms
Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study. (PubMed, Signal Transduct Target Ther)
Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group, while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group. These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL, warranting further investigation.
P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
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IL10 (Interleukin 10) • IL6R (Interleukin 6 receptor)
|
Rituxan (rituximab) • Tyvyt (sintilimab) • temozolomide • methotrexate • methotrexate IV
2ms
Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: a case report and a review of the literature. (PubMed, Brain Tumor Pathol)
The patient received whole-brain radiotherapy following the failure of high-dose methotrexate...This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.
Review • Journal
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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methotrexate • methotrexate IV
3ms
Glucarpidase After High-Dose Methotrexate in Patients With Osteosarcoma (clinicaltrials.gov)
P1, N=12, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting
Enrollment closed
|
methotrexate IV
3ms
Intestinal mucositis, systemic inflammation and bloodstream infections following high-dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the NOPHO ALL 2008 protocol and the ALLTogether1 protocol. (PubMed, Int J Cancer)
These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.
Journal
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CCL20 (C-C Motif Chemokine Ligand 20) • CRP (C-reactive protein)
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methotrexate • methotrexate IV
3ms
Successful treatment of hemophagocytic intravascular large B-cell lymphoma with CNS involvement with BTK inhibitor combined with rituximab and high-dose methotrexate. (PubMed, Ther Adv Hematol)
Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.
Journal
|
IL1R1 (Interleukin 1 receptor, type I)
|
Rituxan (rituximab) • Brukinsa (zanubrutinib) • methotrexate • methotrexate IV
3ms
Local vs Systemic Methotrexate in Management of Uterine Ectopic Pregnancy (clinicaltrials.gov)
P=N/A, N=34, Recruiting, Tanta University | Not yet recruiting --> Recruiting
Enrollment open
|
methotrexate IV
3ms
New trial
|
methotrexate IV
3ms
Blinatumomab Plus Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating B-ALL (clinicaltrials.gov)
P2, N=20, Recruiting, First Affiliated Hospital of Zhejiang University
New P2 trial
|
Venclexta (venetoclax) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • dexamethasone • Oncaspar liquid (pegaspargase) • dexamethasone injection • methotrexate IV
4ms
Generalized Telangiectasia as a Hallmark of Intravascular Lymphoma: A Case Report and Literature Review. (PubMed, Healthcare (Basel))
She was diagnosed with intravascular large B-cell lymphoma (IVLBCL) and went into remission of the skin manifestations after seven courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and four courses of intravenous high-dose methotrexate (HD MTX). From a review of the literature, we found that generalized telangiectasia is a remarkable manifestation of intravascular lymphoma, and the differential diagnosis of intravascular lymphoma and panniculitis or vasculitis is very important. When the diagnosis is confusing, multiple skin biopsies are useful.
Review • Journal
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CD20 (Membrane Spanning 4-Domains A1)
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • methotrexate IV
4ms
VALIDATE: A Phase I/II Study to Investigate the Use of VORAXAZE™ as Intended Intervention in Patients With CNSL (clinicaltrials.gov)
P1/2, N=18, Active, not recruiting, Charite University, Berlin, Germany | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date
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methotrexate IV
4ms
Primary Diffuse Large B-Cell Lymphoma of the Breast with MYC and BCL2 Rearrangements with Terminal Deoxynucleotidyl Transferase Expression: A Case Report. (PubMed, Case Rep Oncol)
She was treated with 6 cycles of R-hyperCVAD/MA (R = rituximab, C = cyclophosphamide, V = vincristine, A = cytarabine, D = dexamethasone, M = methotrexate) and intrathecal chemotherapy (IT CT)...Primary DLBCL of the breast with rearrangement of MYC and BCL2 and tdt expression is an aggressive disease not very well studied that needs to be treated with an intensive CT and CNS prophylaxis. Stem cell transplant could be given after first remission.
Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • CD79A (CD79a Molecule) • MME (Membrane Metalloendopeptidase)
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Rituxan (rituximab) • cytarabine • cyclophosphamide • vincristine • dexamethasone • methotrexate IV
4ms
Systematic review: genetic polymorphisms in the pharmacokinetics of high-dose methotrexate in pediatric acute lymphoblastic leukemia patients. (PubMed, Cancer Chemother Pharmacol)
Among these, variations in SLCO1B1 have the most significant and consistent impact on methotrexate clearance. These implicated variants may contribute to the precision and tailoring of HD-MTX treatment in pediatric ALL patients.
PK/PD data • Review • Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1) • MTHFR (Methylenetetrahydrofolate Reductase) • ABCC2 (ATP Binding Cassette Subfamily C Member 2)
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methotrexate • methotrexate IV
4ms
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis (clinicaltrials.gov)
P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial completion date: Sep 2024 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Oct 2024
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
methotrexate IV
4ms
Ruxolitinib With Tacrolimus and Methotrexate for the Prevention of Graft Versus Host Disease in Pediatric and Young Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome (clinicaltrials.gov)
P2, N=40, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Oct 2027 --> Nov 2030 | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Oct 2027 --> Nov 2030
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date
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Jakafi (ruxolitinib) • methotrexate • methotrexate IV
5ms
Untargeted metabolic profiling of high-dose methotrexate toxicity shows alteration in betaine metabolism. (PubMed, Drug Chem Toxicol)
Among them, L-arginine, homocysteine, and betaine were significantly upregulated, suggesting their possible association with cardiac tissue injury. Overall, we provided evidence for using untargeted metabolomics to identify novel metabolites associated with HDMTX cardiac toxicity.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha)
|
methotrexate • methotrexate IV
5ms
Pembrolizumab and Combination Chemotherapy Before Surgery for the Treatment of Muscle-Invasive Bladder Cancer (clinicaltrials.gov)
P2, N=17, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting
Enrollment closed • Surgery
|
Keytruda (pembrolizumab) • cisplatin • doxorubicin hydrochloride • methotrexate • daunorubicin • vinblastine • Neulasta (pegfilgrastim) • Neupogen (filgrastim) • methotrexate IV
5ms
Prognostic Value of CSF IL-10 at Early Assessment of Induction Chemotherapy in Primary CNS Lymphomas: A LOC Network Study. (PubMed, Neurology)
Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.
Retrospective data • Journal
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IL10 (Interleukin 10)
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methotrexate • methotrexate IV
6ms
GENE EXPRESSION PROFILING OF RELAPSED AND REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA REVEALS ENRICHMENT OF IMMUNE SIGNALING PATHWAYS (EHA 2024)
Induction therapy consistedof methotrexate, vincristine, procarbazine (MVP) with (40...1%) rituximab (R-MVP)... We observed a significant proportion of "high-risk" PCNSL characterized by dismal prognosis and tumorupregulation of immune checkpoints TIGIT and HAVCR2, supporting immune evasion as a disease mechanism. This represents a potential avenue for integrating immunotherapy into existing treatment regimens.
Gene expression profiling • IO biomarker
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CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • MVP (Major Vault Protein) • WNT11 (Wnt Family Member 11)
|
nCounter® PanCancer IO 360™ Panel
|
Rituxan (rituximab) • vincristine • Matulane (procarbazine hydrochloride) • methotrexate IV
6ms
Retrospective Registry Study of Patients With Cancer Treated With High-dose Methotrexate (clinicaltrials.gov)
P=N/A, N=1000, Recruiting, Protherics Medicines Development Limited | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Aug 2024
Trial completion date • Trial primary completion date
|
methotrexate IV
7ms
Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma (clinicaltrials.gov)
P2, N=137, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024
Trial completion • Trial completion date • Combination therapy
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ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • Adcetris (brentuximab vedotin) • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • methotrexate IV
7ms
Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=32, Suspended, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025
Trial completion date • Trial primary completion date
|
Opdivo (nivolumab) • Rituxan (rituximab) • lenalidomide • methotrexate • ABP 206 (nivolumab biosimilar) • Mabtas (rituximab biosimilar) • methotrexate IV
7ms
Trial completion • Trial completion date • Surgery
|
cisplatin • carboplatin • cyclophosphamide • etoposide IV • vincristine • leucovorin calcium • thiotepa • Neupogen (filgrastim) • methotrexate IV
7ms
Trial completion date • Metastases
|
Gilotrif (afatinib) • methotrexate IV
8ms
NCI-2018-01752: Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant (clinicaltrials.gov)
P2, N=68, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
|
cyclophosphamide • methotrexate • fludarabine IV • thiotepa • busulfan • methotrexate IV
8ms
Risk factors associated with high-dose methotrexate induced toxicities. (PubMed, Expert Opin Drug Metab Toxicol)
This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
Review • Journal
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • MTHFR (Methylenetetrahydrofolate Reductase) • ARID5B (AT-Rich Interaction Domain 5B) • PNPLA3 (Patatin Like Phospholipase Domain Containing 3)
|
UGT1A1*1*1
|
methotrexate • methotrexate IV
9ms
The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation. (PubMed, Drug Des Devel Ther)
In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects. The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.
Preclinical • Journal
|
IL6 (Interleukin 6)
|
Daliresp (roflumilast) • methotrexate IV
9ms
The Effects of Genetic Polymorphism on Toxicity and Pharmacokinetics of Methotrexate in Egyptian Adult Patients with Leukaemia or Lymphoma. (PubMed, Xenobiotica)
GGH mutation was mainly concerned with anemia. Pharmacogenetic testing are recommended to optimize MTX therapy.
PK/PD data • Journal
|
MTHFR (Methylenetetrahydrofolate Reductase)
|
MTHFR C677T
|
methotrexate • methotrexate IV
9ms
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors (clinicaltrials.gov)
P4, N=250, Active, not recruiting, Nationwide Children's Hospital | Recruiting --> Active, not recruiting
Enrollment closed
|
cisplatin • carboplatin • cyclophosphamide • etoposide IV • vincristine • thiotepa • methotrexate IV
9ms
Trial initiation date
|
Jakafi (ruxolitinib) • methotrexate • methotrexate IV
9ms
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis (clinicaltrials.gov)
P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Feb 2024 --> Jun 2024
Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 positive • HER-2 negative • ER negative • ER positive + PGR positive • PGR negative
|
methotrexate IV
9ms
Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=32, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
Trial suspension
|
Opdivo (nivolumab) • Rituxan (rituximab) • lenalidomide • methotrexate • ABP 206 (nivolumab biosimilar) • Mabtas (rituximab biosimilar) • methotrexate IV
9ms
Trial completion
|
CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr t(11;14) • CD20 expression
|
cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine • Arzerra (ofatumumab) • Starasid (cytarabine ocfosfate) • dexamethasone injection • methotrexate IV
10ms
LCI-HEM-PCNSL-RMPV-001: Nivolumab Consolidation in Older (≥ 65) Patients With Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=14, Active, not recruiting, Wake Forest University Health Sciences | Phase classification: P1b --> P1
Phase classification
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 positive
|
Opdivo (nivolumab) • methotrexate IV
10ms
Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy. (PubMed, World J Clin Oncol)
Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.
Clinical data • Journal • Combination therapy
|
PIM1 (Pim-1 Proto-Oncogene)
|
PIM1 mutation
|
Brukinsa (zanubrutinib) • methotrexate • methotrexate IV