methotrexate IV

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

P3, N=70, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Mar 2024

P3, N=340, Active, not recruiting, Boehringer Ingelheim | Trial completion date: May 2024 --> Aug 2024

P2, N=68, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

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.

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.

GGH mutation was mainly concerned with anemia. Pharmacogenetic testing are recommended to optimize MTX therapy.

P4, N=250, Active, not recruiting, Nationwide Children's Hospital | Recruiting --> Active, not recruiting

P2, N=40, Not yet recruiting, City of Hope Medical Center | Initiation date: Jan 2024 --> Jun 2024

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Feb 2024 --> Jun 2024

P1, N=32, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=37, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed

P1, N=14, Active, not recruiting, Wake Forest University Health Sciences | Phase classification: P1b --> P1

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.

P1, N=18, Terminated, Fred Hutchinson Cancer Center | N=40 --> 18 | Trial completion date: Dec 2023 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Jul 2023; Closed per SRC Low Accrual Policy

P2, N=40, Recruiting, Fred Hutchinson Cancer Center

Evidence supporting the use of intravenous methotrexate (MTX) or arabinoside (AraC) in high-risk patients is growing, however, the use of other agents remains to be defined...All patients are need to receive IT thiotepa 10 mg and dexamethasone 5 mg on day 1 of each cycle of chemotherapy for at least 4 cycles...6%) patients received rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP), 5 (18...1%) patients received BTK inhibitor, lenalidomide with rituximab (ZR2) followed by RCHOP, and 4 (14...ConclusionProphylactic intrathecal thiotepa is an effective and side-effects manageable measure for preventing secondary central nervous system involvement in high-risk DLBCL. Longer follow-up and larger-scale prospective trial is needed to testify this measure.

PTL may benefit from HD-MTX in preventing relapse, while alternative treatments should be explored for DLBCL-T. Future studies should consider PTL and DLBCL-T as separate entities to better understand their characteristics and optimize treatment strategies.

The HCT regimen involved busulfan 3. 2 mg/kg on days -5, -4, thiotepa 250 mg/m 2 on days -7 and -6, cytarabine 2g/m 2 q12h on days -3 and -2, followed by reinfusion of stem cells on day 0... The R-MTO induction treatment has demonstrated notable efficacy in achieving higher response rates among patients with PCNSL, and the associated adverse events are manageable.

5 - 5 g/m 2 and Asp 1000-2000 UI/m 2), patients with BL received modified Rituxumab (R)-BFM protocol (MTX 1... The analysis ofMTHFR polymorphisms in adult patients is useful in identifying patients at higher risk for transaminitis, providing a biological parameter to integrate with hepatosteatosis, liver stiffness evaluation and BMI, for a comprehensive hepatic baseline evaluation. Patients at higher risk for hepatic complications may benefit from MTX dose reduction with no impact on disease outcome.

P2, N=120, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Aug 2026 --> Dec 2028 | Trial primary completion date: Aug 2025 --> Dec 2026

Survivors of DLBCL have an increased risk of secondary primary malignancies; previous studies found that incidence of acute myeloid leukaemia (AML) nearly doubled in the post rituximab era...Due to severe chronic obstructive pulmonary disease, autologous transplant was excluded, thus request for Tafasitamablenalidomide under an extended access program was sent and approved in July 2022. After two cycles, lenalidomide was reduced because of grade 3-4 neutropenia poorly responsive to G-CSF...Patient started decitabine plus venetoclax protocol that is still ongoing...Patient has been candidated to allogenic transplant and azacitidine is now ongoing...Recently, the risk of SMN is also of particular concern in the CAR-T receivers. In conclusion a better comprehension of SPM/SMN pathology in DLBCL survivors is needed in order to guide the best “tailored” surveillance.

P2, N=40, Not yet recruiting, City of Hope Medical Center

P1, N=12, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=17, Recruiting, University of Washington | Trial primary completion date: Oct 2023 --> Apr 2024

The induction regimen comprised reduced intensity chemotherapy (idarubicin 8 mg/m2 on day 1, vindesine 4 mg on day 1, and dexamethasone 9 mg/m2/day from day 1-7) followed by 2 weeks of blinatumomab (9 ug/day from day 8-14, 28 ug/day from day 15-21)...Consolidation therapy was given after achieving ORR with recommended multidrug combination chemotherapy (including high-dose methotrexate or cytarabine combined with asparaginase) or alternating with blinatumomab (28 ug/day for 28 days)... These preliminary results indicate that the reduced intensity chemotherapy followed by blinatumomab is an effective regimen in adults with newly diagnosed Ph-negative BCP-ALL, resulting in favorable response rates, deep remission, and low-grade treatment-related AEs. These promising findings may provide a rationale for integrating blinatumomab into future induction therapy recommendations.

Pts received hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...One pt discontinued blinatumomab due to a related adverse event (grade 2 encephalopathy and dysphasia). No pts discontinued INO due to toxicity, and no cases of veno-occlusive disease have been observed.

Pts receive isavuconazole as fungal prophylaxis throughout therapy... Pts with ibrutinib-responsive SCNSL achieve a high rate of CR to TEDDI-R, and preliminary data suggest these remissions are durable. Most ibrutinib-responsive tumors are CD10-negative and enriched for MCD and BN2. TEDDI-R can be delivered as an outpatient to pts of all ages.

We designed a phase II trial (GIMEMA LAL2317) for adult Ph- CD19+ B-lineage ALL (Ph- B-ALL) consisting of a pediatric chemotherapy backbone – with dose adjustment in patients >55 years – to which 2 cycles of blinatumomab were added, the first after early consolidation cycle 3 (high-dose methotrexate and Ara-C) and the second after late consolidation cycle 6...Importantly, at TP3 the MRD status no longer impacted, highlighting the therapeutic role of blinatumomab, as observed in Ph+ ALL. Finally, the Ph-like signature retains its negative prognostic impact, suggesting that a combination strategy, similar to that in place for Ph+ ALL, is required.

CONCLUSIONS The SRMT regimen as frontline treatment for PCNSL is highly efficacious and well tolerated. (Chinese Clinical Trial Registry number: ChiCTR1900027433).

Combining Selinexor(1μM) with ICP-022(2μM), a BTKi, resulted in more notable inhibition of the above tumor signaling pathways...2 others were on maintenance therapy with Selinexor combined with Zanubrutinib, one of them has completed the two-year maintenance treatment and maintained sustained remission till now... This is the first report describing that Selinexor combined with BTKi can synergistically inhibit the DLBCL tumor signaling pathway and repairing the immune microenvironment. Correspondingly, in treatment of central DLBCL patients, the novel therapeutic strategy of MSZ regimen has achieved impressive results, with a CRR of 100%. Most patients attained early and rapid deep remissions with durable efficacy.

For those who received systemic therapy, all incorporated high-dose methotrexate with the median dose delivered of 3.5g/m2 per cycle and rituximab was incorporated in 48%... To our knowledge, this is the largest international multicenter cohort of patients with isolated PVRL reported in the modern era. The apparent improvement in OS compared with historical cohorts may reflect improvements in therapy in the recent decade, and incorporation of systemic therapy in frontline management demonstrated a trend to improved OS. However, high rates of CNS relapse continue to be a challenge.

The novel induction treatment of MIT achieved encouraging responses in newly diagnosed PCNSL patients with acceptable toxicities. The early clearance of ctDNA in CSF may be related to favorable survival.

All 24 patients were treated with a BTK inhibitor (Zanubrutinib 160mg bid, or Orelabrutinib 150mg qd), of whom, 9 VRL patients were also treated with intravitreal methotrexate injection (0.4mg/ time, weekly ×12 times → monthly ×9 times) concurrently, and the remaining 15 patients did not receive any antitumor therapy other than BTK inhibitors... This is the largest report regarding the use of BTK inhibitors in VRL patients. BTK inhibitor has a rapid local control effect on VRL and is well tolerated. However, BTK inhibitors monotherapy has unsatisfied preventive effect on the CNS, and it is still necessary to explore the value of combinational therapy, such as combined BTK inhibitors and high-dose methotrexate.

Patient between the ages of 30 and 70 with newly diagnosed BCR::ABL1 negative B-lineage ALL were enrolled and initially received 2.5 months of combination induction chemo utilizing a BFM-like regimen adapted from the E2993/UKALLXII clinical trial, with pegaspargase (after induction only for patients >=55 years of age) and addition of rituximab for CD20 positive patients... The addition of blinatumomab to consolidation chemotherapy resulted in a significantly better overall survival compared to chemotherapy alone in pts with newly diagnosed B-lineage ALL who were MRD negative after intensification. This represents a new standard of care for pts aged 30-70 years with BCR::ABL1 negative ALL. The optimal dose and number of cycles is however unknown.

In our multi-center clinical trial, we observed excellent outcomes in a diverse group of patients nationwide. Using the NCI criteria for stratification, a significant number of patients were categorized into the SR. Additionally, introducing L-ASP during early consolidation decreased the number of MRD-positive patients, which subsequently reduced the subset needing allo-HCT.

Among the 348 patients, 62 (18%) received DA-EPOCH-R/HD-MTX, and 286 (82%) were treated with other R-chemo, such as R-CHOP (n = 254)... Our results confirmed favorable survival in the phase II study of DA-EPOCH-R/HD-MTX in clinical settings. DA-EPOCH-R/HD-MTX and IT MTX were associated with longer OS of patients with CD5+ DLBCL in our study cohort, warranting further investigation.

In terms of frontline-treatment, 21 patients (95%) had received HDMTX + procarbazine + vincristine, and rituximab was administered in 73% (16/22) of patients...CONCLUSION Given that only restricted treatment strategies are available for relapse PCNSL patients, our study suggests that nivolumab can be a suitable option for the disease. Further studies are warranted to determine predictive biomarkers for nivolumab treatment given the excellent survival duration in responders.

Sys-CNS pts also received R-CHOP or DA-R-EPOCH while R-Sys-CNS pts received R-Polatuzumab or Polatuzumab-R-Bendamustine...Pts with simultaneous CNS and systemic relapse had worse OS. Prospective studies are needed to evaluate optimal treatment for SCNSL.

P3, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Aug 2023 --> Aug 2024

Participants must not have received any prior cytotoxic chemotherapy or rituximab for treatment of the newly diagnosed DLBCL except for the pre- phase treatment...High-dose intravenous methotrexate is not allowed...Five of the 27 participants assessed for adverse events on the R-miniCHOP arm experienced Grade 4 hematologic toxicities. An additional six participants on the CC-486 + R- miniCHOP arm and 10 participants on the R- miniCHOP arm experienced Grade 3 toxicities as maximum degree.

Participants must not have received any prior cytotoxic chemotherapy or rituximab for treatment of the newly diagnosed DLBCL except for the pre- phase treatment...High-dose intravenous methotrexate is not allowed...Five of the 27 participants assessed for adverse events on the R-miniCHOP arm experienced Grade 4 hematologic toxicities. An additional six participants on the CC-486 + R- miniCHOP arm and 10 participants on the R- miniCHOP arm experienced Grade 3 toxicities as maximum degree.