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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Complete response rate
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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-
- •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.
排除标准
- •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/mm
- •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.
研究组 & 干预措施
TPG therapy
All enrolled patients will receive the same study therapy for the first four 21-day cycles, followed by the primary endpoint evaluation, and subsequent response-adapted therapy. After 4 cycles, the primary endpoint will be assessed by using positron emission tomography/computed tomography (PET-CT) based Lugano criteria. Subsequent therapy will be determined at that time, guided by the response assessment. Patients in complete response or with a partial metabolic response and a negative minimal residual disease (MRD) assay will continue with subsequent cycles of TPG immunotherapy. Patients who do not achieve these criteria will transition to standard immunochemotherapy, which will be delivered according to institutional standards.
干预措施: Glofitamab (Drug)
TPG therapy
All enrolled patients will receive the same study therapy for the first four 21-day cycles, followed by the primary endpoint evaluation, and subsequent response-adapted therapy. After 4 cycles, the primary endpoint will be assessed by using positron emission tomography/computed tomography (PET-CT) based Lugano criteria. Subsequent therapy will be determined at that time, guided by the response assessment. Patients in complete response or with a partial metabolic response and a negative minimal residual disease (MRD) assay will continue with subsequent cycles of TPG immunotherapy. Patients who do not achieve these criteria will transition to standard immunochemotherapy, which will be delivered according to institutional standards.
干预措施: Obinutuzumab (Drug)
TPG therapy
All enrolled patients will receive the same study therapy for the first four 21-day cycles, followed by the primary endpoint evaluation, and subsequent response-adapted therapy. After 4 cycles, the primary endpoint will be assessed by using positron emission tomography/computed tomography (PET-CT) based Lugano criteria. Subsequent therapy will be determined at that time, guided by the response assessment. Patients in complete response or with a partial metabolic response and a negative minimal residual disease (MRD) assay will continue with subsequent cycles of TPG immunotherapy. Patients who do not achieve these criteria will transition to standard immunochemotherapy, which will be delivered according to institutional standards.
干预措施: Polatuzumab vedotin (Drug)
TPG therapy
All enrolled patients will receive the same study therapy for the first four 21-day cycles, followed by the primary endpoint evaluation, and subsequent response-adapted therapy. After 4 cycles, the primary endpoint will be assessed by using positron emission tomography/computed tomography (PET-CT) based Lugano criteria. Subsequent therapy will be determined at that time, guided by the response assessment. Patients in complete response or with a partial metabolic response and a negative minimal residual disease (MRD) assay will continue with subsequent cycles of TPG immunotherapy. Patients who do not achieve these criteria will transition to standard immunochemotherapy, which will be delivered according to institutional standards.
干预措施: Tafasitamab (Drug)
结局指标
主要结局
Complete response rate
时间窗: 3 months after starting therapy
• Complete response (CR) rate after 4 cycles of TPG therapy, evaluated by PET-CT using Lugano criteria
Rate of toxicities
时间窗: From the day when informed consent is obtained until 90 days following the last administration of study treatment.
Occurrence and severity of adverse events will be examined throughout the treatment using the Common Terminology Criteria for Adverse Events (CTCAE) v6.0, except cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) will be assessed using the American Society of Transplantation and Cellular Therapy (ASTCT) criteria
次要结局
- Progression-free survival(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(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(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(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(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(At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically 9 months from the start).)
- Patient-centered measure of treatment burden(At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically 9 months from the start of therapy).)
- Minimal residual disease(At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy (typically 9 months from the start), then every 6 months until 2 years of follow up.)
研究者
Adam Olszewski
Associate Professor of Medicine
Brown University