Zevalin (ibritumomab tiuxetan)

However, despite their therapeutic efficacy, Bexxar® was withdrawn from the market by the manufacturer in 2014 due to limited commercial demand and Zevalin® has had very limited to no availability of late. I-131 rituximab is used to a limited extent in Australia, India and other countries, as well. But has RIT of NHL been (perhaps prematurely) left for dead by many? Given the current great clinical and commercial interest in radiopharmaceutical therapies of cancer, notably PSMA and SSTR targeting agents in prostate and neuroendocrine cancers, can radioimmunotherapy of NHL-like the mythical Phoenix-now rise from its ashes in an even better form to fly higher, faster, farther and longer than before?

P2, N=41, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P2, N=159, Completed, SWOG Cancer Research Network | Active, not recruiting --> Completed

Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations.

P3, N=20, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Nov 2023

P2, N=41, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2023 --> Dec 2023

Addition of Zevalin to Flu/Mel is safe and effective in high-risk NHL and met the prespecific endpoint. Results were suboptimal in patients with DLBCL.

P2, N=159, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jun 2023 --> Oct 2023

For instance, the theranostic armamentarium for the referring hematooncologist now includes Y-ibritumomab tiuxetan for refractory low-grade follicular lymphoma or transformed B-cell non-Hodgkin lymphoma, as well as I-tositumomab for rituximab-refractory follicular lymphoma. Moreover, the first interim results of the SIERRA phase III trial reported beneficial effects from the use of I-anti-CD45 antibodies (Iomab-B) in refractory or relapsed acute myeloid leukemia...As an integral part of the treatment plan, such radioligand therapy-mediated myeloablation also allows one to line up patients for stem cell transplantation, which leads to successful engraftment during the further treatment course. In this continuing education article, we provide an overview of the current advent of theranostics in hematooncology and highlight emerging clinical applications.

No abstract available

P2, N=41, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Jun 2023

P2, N=20, Active, not recruiting, Joseph Tuscano | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Apr 2022 --> Apr 2023

P3, N=20, Active, not recruiting, Mayo Clinic | Trial primary completion date: Jan 2023 --> Jan 2022

Other than that, a resistance mechanism to rituximab emerged by inducing a failure in the apoptosis mechanism...Here came the development of 90Y-ibritumomab tiuxetan and 131I-tositumomab. After it, humanized anti-CD20 emerged ofatumumab, IMMU106 (veltuzumab) in 2005, and ocrelizumab which are considered as second generation anti-CD20 and 3 generation anti-CD20 include AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutuzumab). Also multiple other agents emerged targeting different surface cell antigens like CD52 (alemtuzumab), CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab], Brentuximab vedotin), CD40 (SGN-40), and CD79b (Polatuzumab). Other agents include MAB targeting T-Cells like mogamulizumab, Denileukin Diftitox and BiTEs or bispecific T cell engagers like Mosunetuzumab, Glofitamab, and Epcoritamab...Another important aspect in immunotherapy is the half-lives of the medication which is an important factor that can influence the evaluation of the response. The MAB treatment showed important benefit in the treatment of iNHL and it continuously shows how rapidly it can develop to provide optimum care and benefit to patients with iNHL.

P2, N=54, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2021 --> Dec 2022

P3, N=20, Active, not recruiting, Mayo Clinic | Trial primary completion date: Jan 2022 --> Jan 2023

P3, N=68, Terminated, Spectrum Pharmaceuticals, Inc | N=400 --> 68 | Active, not recruiting --> Terminated; due to low recruitment rate that would have led to a long study duration.

P2, N=46, Completed, Southwest Oncology Group | Active, not recruiting --> Completed

In particular, two monoclonal antibodies raised against CD20, that is Zevalin (Y-ibritumomab-tiuxetan) and Bexxar (I-tositumomab) received FDA approval for the treatment of relapsing/refractory indolent or transformed NHLs...However, its use in the clinical setting is still debated and, in case of relapse after optimized rituximab-containing regimens, the efficacy of RIT at standard dosage is suboptimal...In contrast, dose-escalation clinical protocols require the assessment of radiopharmaceutical biodistribution and dosimetry before the therapeutic injection, as dose constrains for critical organs may be exceeded when RIT is administered at high activities. The aim of the present study was to review and discuss the internal dosimetry protocols that were adopted for non-standard RIT administration in the myeloablative setting before hematopoietic stem cell transplantation in patients with NHLs.

P2, N=1, Terminated, University of Southampton | N=100 --> 1 | Recruiting --> Terminated; no information

P2, N=20, Active, not recruiting, Joseph Tuscano | Recruiting --> Active, not recruiting | Trial completion date: Jun 2022 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Apr 2022

Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine, and low-dose TBI followed by an HLA-matched allo-HCT was feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint while producing nonhematologic toxicities comparable to standard RIC regimens. (Registered at ClinicalTrials.gov as NCT01434472).

P=N/A, N=400, Completed, Spectrum Pharmaceuticals, Inc | Recruiting --> Completed

P3, N=20, Active, not recruiting, Mayo Clinic | Trial primary completion date: Jun 2020 --> Jan 2022

P3, N=20, Active, not recruiting, Mayo Clinic | Suspended --> Active, not recruiting

Patient-specific outpatient Y ibritumomab tiuxetan RIT with myeloablative doses of RIT up to a targeted 30.5 Gy to the liver is feasible, guided by prospective SPECT/CT + planar imaging with the theranostic pair of In and Y anti-CD20, with outpatient autologous stem cell transplant support. Administered activity over 5 times the standard FDA-approved activity was well-tolerated. The non-hematopoietic MTD in this study exceeds 28 Gy to the liver. Initial tumor responses were common at all dose levels. This study supports the feasibility of organ dosimetry-driven patient-specific dose escalation in the treatment of NHL with stem cell transplant and provides additional information on the radiation tolerance of the normal liver to radiopharmaceutical therapy.

P2, N=20, Terminated, Fred Hutchinson Cancer Research Center | Active, not recruiting --> Terminated; Terminated due to insufficient funding

P2, N=39, Completed, Dartmouth-Hitchcock Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2020 --> Apr 2021 | Trial primary completion date: Jun 2014 --> Jan 2021

P2, N=46, Active, not recruiting, Southwest Oncology Group | Trial completion date: Nov 2020 --> Nov 2021

P2, N=54, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2019 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Dec 2021

P2, N=49, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2020 --> Feb 2021 | Trial primary completion date: Aug 2020 --> Feb 2021

Based on the log-rank test of factors associated with the progression-free survival (PFS), ≥2 previous treatment regimens was significantly associated with a poor prognosis (P<0.05). The SUV on In-IT SPECT/CT may be a good predictor of the clinical response to Y-IT therapy.

While outpatient, patients received rituximab 250mg/m2 followed by 90Y-Ibritumomab tiuxetan (1.5 mCi/kg 90Y capped at 120mCi) (day -14), fludarabine 30mg/m2 (days -4 to -2), then 2Gy TBI and HLA-matched PBSC allo-HCT. Cyclosporine and mycophenolate mofetil were used for acute GvHD prophylaxis... Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine and low-dose TBI followed by an HLA-matched allo-HCT appears feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint of 50% 1-year PFS. Short and long­-term non-hematologic toxicity appear comparable to standard RIC regimens.

While outpatient, patients received rituximab 250mg/m2 followed by 90Y-Ibritumomab tiuxetan (1.5 mCi/kg 90Y capped at 120mCi) (day -14), fludarabine 30mg/m2 (days -4 to -2), then 2Gy TBI and HLA-matched PBSC allo-HCT. Cyclosporine and mycophenolate mofetil were used for acute GvHD prophylaxis... Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine and low-dose TBI followed by an HLA-matched allo-HCT appears feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint of 50% 1-year PFS. Short and long­-term non-hematologic toxicity appear comparable to standard RIC regimens.

While outpatient, patients received rituximab 250mg/m2 followed by 90Y-Ibritumomab tiuxetan (1.5 mCi/kg 90Y capped at 120mCi) (day -14), fludarabine 30mg/m2 (days -4 to -2), then 2Gy TBI and HLA-matched PBSC allo-HCT. Cyclosporine and mycophenolate mofetil were used for acute GvHD prophylaxis... Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine and low-dose TBI followed by an HLA-matched allo-HCT appears feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint of 50% 1-year PFS. Short and long­-term non-hematologic toxicity appear comparable to standard RIC regimens.

While outpatient, patients received rituximab 250mg/m2 followed by 90Y-Ibritumomab tiuxetan (1.5 mCi/kg 90Y capped at 120mCi) (day -14), fludarabine 30mg/m2 (days -4 to -2), then 2Gy TBI and HLA-matched PBSC allo-HCT. Cyclosporine and mycophenolate mofetil were used for acute GvHD prophylaxis... Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine and low-dose TBI followed by an HLA-matched allo-HCT appears feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint of 50% 1-year PFS. Short and long­-term non-hematologic toxicity appear comparable to standard RIC regimens.

While outpatient, patients received rituximab 250mg/m2 followed by 90Y-Ibritumomab tiuxetan (1.5 mCi/kg 90Y capped at 120mCi) (day -14), fludarabine 30mg/m2 (days -4 to -2), then 2Gy TBI and HLA-matched PBSC allo-HCT. Cyclosporine and mycophenolate mofetil were used for acute GvHD prophylaxis... Mega-dose 90Y-Ibritumomab tiuxetan, fludarabine and low-dose TBI followed by an HLA-matched allo-HCT appears feasible, safe, and effective in treating aggressive BCL, exceeding the prespecified endpoint of 50% 1-year PFS. Short and long­-term non-hematologic toxicity appear comparable to standard RIC regimens.

P3, N=20, Suspended, Mayo Clinic | N=128 --> 20

P3, N=128, Suspended, Mayo Clinic | Recruiting --> Suspended

P2, N=20, Recruiting, Joseph Tuscano | Trial completion date: Dec 2020 --> Jun 2022 | Trial primary completion date: Jun 2020 --> Dec 2021

The standard treatment approaches have been either 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (RCHOP), closely followed by involved field radiation (IFRT) based on SWOG S8736 and S0014, or 6 cycles of RCHOP based on extrapolation from the Mabthera International Trial (MInT) and advanced-stage DLBCL trials...NCTN study S1001 built on BC Cancer experience and prior SWOG study S0313 which demonstrated promising PFS with the radioimmunotherapy agent ibritumomab tiuxetan.9 Patients had stage I/II non-bulky (< 10 cm) disease as defined by PET...The best therapy for a minority of patients with positive interim PET scan needs to be studied further but could include radiation. Competing risks of death in older patients with limited-stage disease may require different means of measuring outcomes than traditional PFS.