TPG: Tafasitamab, Polatuzumab Vedotin, and Glofitamab as First-line Therapy for Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

Официальное название

TPG: a Phase 2 Trial of Polatuzumab Vedotin, Glofitamab, and Tafasitamab as Chemotherapy-sparing First-line Therapy for Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

Обзор

This is a single-center, phase 2, open-label clinical trial of a novel combination of polatuzumab vedotin, glofitamab, and tafasitamab (TPG) as first-line treatment of patients with diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL).

Вмешательства

• Препарат Tafasitamab
  Cytolytic monoclonal antibody targeting CD19.
• Препарат Polatuzumab vedotin
  CD79b-targeting antibody-drug conjugate
• Препарат Glofitamab
  CD20xCD3 bispecific antibody
• Препарат Obinutuzumab
  Anti-CD20 monoclonal antibody

Первичные конечные точки

• Complete response rate [Срок оценки: 3 months after starting therapy]
• Rate of toxicities [Срок оценки: From the day when informed consent is obtained until 90 days following the last administration of study treatment.]

Вторичные конечные точки (8)

• Progression-free survival [Срок оценки: PFS will be measured from the day of the registration on study until the end of follow up, for up to 5 years]
• Event-free survival [Срок оценки: EFS will be measured from the day of the registration on study until the end of follow up, for up to 5 years]
• Overall survival [Срок оценки: OS will be measured from the day of the registration on study until the end of follow up, for up to 5 years]
• Duration of response [Срок оценки: Duration of response will be measured from the day of the first response recored on study until the end of follow up, for up to 5 years]
• Duration of complete response [Срок оценки: Duration of complete response will be measured from the first response assessment showing a complete response until the end of follow up, up to 5 years.]
• Health-related quality of life [Срок оценки: At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically after 9 months from the start). FACT-Lym has a score range of 0 to 88 and the higher scores indicate worse HR-QOL]
• Patient-centered measure of treatment burden [Срок оценки: At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically after 9 months from the s. The instrument has a score range 8 to 40 and higher scores indicate better functional status.]
• Minimal residual disease [Срок оценки: At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy (typically after 9 months from the start), then every 6 months until 2 years of follow up.]

Критерии участия

Критерии включения

• Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures.
• Age ≥18 years.
• Histologically confirmed diagnosis of DLBCL, or HGBL, according to 5th edition WHO classification. Eligible WHO entities include:

• Diffuse large B-cell lymphoma, not otherwise specified (NOS)
• T-cell/histiocyte-rich large B-cell lymphoma
• DLBCL/HGBL with MYC and BCL2 rearrangements
• Large B-cell lymphoma with IRF4 rearrangement
• HGBL with 11q aberration
• EBV-positive diffuse large B-cell lymphoma
• DLBCL associated with chronic inflammation
• Primary large B-cell lymphoma of immune-privileged sites
• Primary cutaneous DLBCL, leg type
• Intravascular large B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• HGBL, NOS
• Grade 3B follicular lymphoma.
• FDG-avid disease by PET-CT Lugano criteria.
• No prior systemic therapy for B-cell lymphoma, except for:

• corticosteroids;
• a single cycle of chemotherapy administered prior to enrollment (to facilitate enrolling patients who require emergent initiation of therapy for rapidly progressive or symptomatic lymphoma);
• prior local radiation therapy;
• prior treatment for indolent lymphoma.
• Performance status ECOG 0, 1, or 2.
• Ability to receive one of the standard chemotherapy regimens for DLBCL/HGBL including attenuated versions, where clinically appropriate
• Required initial laboratory values: (unless due to underlying lymphoma):

• absolute neutrophil count ≥1.0 x 109/L,
• platelet count ≥75 x 109/L.
• creatinine ≤ 1.5 mg/dL or glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula
• total bilirubin ≤ 1.5 × institution upper limit of normal (ULN) unless attributable to Gilbert's disease
• AST and ALT ≤ 3 × institution ULN.
• Negative antigen or PCR test for SARS-CoV-2.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) and refrain from donating eggs or sperm throughout the treatment and for 3 months after the last dose of trial therapy.

Критерии исключения

• Pregnancy, breast-feeding, or prisoner status.
• Central nervous system involvement by the lymphoma.
• Prior solid organ transplantation or allogeneic stem cell transplantation.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.
• Known NYHA class 3/4 congestive heart failure, left ventricular ejection fraction (LVEF) <30%, or active ischemic heart disease.
• Chronic obstructive pulmonary disease (COPD) requiring continuous oral corticosteroids or chronic oxygen.
• Grade >1 peripheral neuropathy.
• Use of systemic immunosuppressive medications (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 2 weeks prior to first dose of study treatment (except as allowed in the inclusion criteria for the management of lymphoma).
• Any of the following conditions:

• active bacterial infection requiring antibiotics
• chronic active Epstein Barr virus (CAEBV) infection
• history of hemophagocytic lymphohistiocytosis (HLH)
• history of Stevens-Johnson syndrome or toxic epidermal necrolysis
• progressive multifocal leukoencephalopathy (PML)
• known active EBV or CMV viremia
• autoimmune disease requiring systemic immunosuppressive therapy
• active myasthenia gravis, myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus erythematosus, inflammatory bowel disease, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• active hepatitis B (HBV) or hepatitis C (HCV) infection. Patients with a positive total/IgG HBV core antibody (HBcAb) are eligible if (1) HBV DNA is documented at screening, (2) they agree to take entecavir or tenofovir, and (3) they agree to undergo periodic DNA testing. Patients with a positive HCV antibody are eligible if a negative polymerase chain reaction (PCR) for HCV is documented.
• HIV infection with a detectable viral load or a CD4 count <200 cells/mm3. Patients (1) with an undetectable viral load and CD4 count >200 cells/mm3 within 6 months prior to enrollment, and (2) on antiretroviral therapy are eligible.
• Administration of a live, attenuated vaccine within 4 weeks before first treatment or anticipation that such a live, attenuated vaccine will be required during the study.
• History of other malignancy that could affect compliance with the protocol or interpretation of the primary endpoint in the judgement of the investigator.
• Any major surgery within 4 weeks before the first dose of treatment.
• Evidence of other significant or uncontrolled medical or psychiatric conditions that could affect compliance with the protocol, in the judgement of the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Rhode Island Hospital — Providence

Идентификаторы

NCT: NCT07502872 · BrUOG-450 · ML46671 · I-000585-25-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗