A Phase II Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 99
- 试验地点
- 5
- 主要终点
- Part 1: Overall Response Rate (ORR) to Pola-Glofit as bridging prior to CAR-T cell infusion
研究概览
简要总结
The PORTAL study will test a new combination of drugs (glofitamab, polatuzumab vedotin and obinutuzumab) in patients with large B-cell lymphoma (LBCL) that has come back (relapsed) or not responded to previous treatment. It will determine how safe and effective the combination of these cancer drugs is in treating LBCL before and after CAR-T cell therapy.
详细描述
This is a phase 2, open label trial conducted in 2 parts.
The overall aim is:
Part 1: To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with relapsed or refractory large B cell lymphomas.
Part 2: To determine the efficacy of Pola-Glofit in patients with relapsed or refractory large B cell lymphomas who have failed to achieve CMR, or progressed after CAR-T cell therapy.
Treatment consists of:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically proven CD20+ LBCL (with CD20 positivity at any timepoint) including diffuse large B cell lymphoma, high grade B cell lymphoma with MYC, BCL2 and/or BCL6 (double/triple hit lymphoma), high grade B cell lymphoma not otherwise specified (NOS), primary mediastinal B-cell lymphoma or transformed follicular lymphoma.
- •Part 1: Relapsed or refractory disease and eligible for CAR T-cell therapy in the UK and in need of systemic bridging in the opinion of the local investigator.
- •Part 2: Failed to achieve CMR (Deauville score 1-3) on PET scan 1-month post CAR-T or progressed at any point post CAR-T (patients in part 2 may have been previously enrolled in Part 1 and responded to Pola-Glofit bridging or be de novo patients who are naïve to this combination)
- •At least one measurable target lesion
- •Patient has recent archival biopsy tissue available or is willing to undergo a new biopsy.
- •ECOG performance status:
- •Part 1: ECOG PS 0/1
- •Part 2: ECOG PS 0-2
- •Life expectancy of ≥ 12 weeks
- •Adequate haematological status.
- •Adequate liver and renal function
- •Negative test for hepatitis B, hepatitis C, HIV and SARS-CoV-2
排除标准
- •Patients with known active infection
- •Current ≥ Grade 2 peripheral neuropathy
- •History of confirmed progressive multifocal leukoencephalopathy
- •Current evidence of CNS lymphoma
- •Patients with another invasive malignancy in the last 2 years
- •Significant history of cardiovascular disease
- •Active autoimmune disease or immune deficiency
- •Severe neurological disorder
- •Uncontrolled tumour-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites
- •Treatment with other standard anti-cancer radiotherapy/chemotherapy including investigational therapy and targeted therapy within 4 weeks prior to cycle 1 day 1
- •Prior solid organ transplantation
- •Prior allogeneic stem cell transplant
- •Autologous SCT within 100 days prior to cycle 1 day 1
- •Any history of immune related ≥ Grade 3 adverse events
- •Ongoing corticosteroid use > 25 mg/day of prednisone or equivalent within 4 weeks prior to study treatment
- •Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
- •Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1 day 1
- •History of severe allergic anaphylactic reactions to chimeric or humanised monoclonal antibodies or recombinant antibody-related fusion proteins.
- •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the obinutuzumab, polatuzumab vedotin and/or glofitamab formulation.
- •Known or suspected history of HLH
研究组 & 干预措施
Part 1
Patients whose large B-cell lymphoma has progressed/not responded to previous treatment and are due to start standard CAR-T therapy.
All patients receive 2 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola). Obinutuzumab pre-treatment is given on cycle 1 day 1.
Patients have a PET-CT scan to check the response after cycle 2. If the scan shows a response and patients are still suitable for CAR-T cell therapy, patients will proceed to receive planned CAR-T therapy and will not receive further Glofit-Pola in Part 1. If not, patients can receive 4 more cycles of glofitamab and polatuzumab vedotin, and then 6 cycles of glofitamab.
干预措施: Glofitamab (Drug)
Part 1
Patients whose large B-cell lymphoma has progressed/not responded to previous treatment and are due to start standard CAR-T therapy.
All patients receive 2 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola). Obinutuzumab pre-treatment is given on cycle 1 day 1.
Patients have a PET-CT scan to check the response after cycle 2. If the scan shows a response and patients are still suitable for CAR-T cell therapy, patients will proceed to receive planned CAR-T therapy and will not receive further Glofit-Pola in Part 1. If not, patients can receive 4 more cycles of glofitamab and polatuzumab vedotin, and then 6 cycles of glofitamab.
干预措施: Polatuzumab vedotin (Drug)
Part 1
Patients whose large B-cell lymphoma has progressed/not responded to previous treatment and are due to start standard CAR-T therapy.
All patients receive 2 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola). Obinutuzumab pre-treatment is given on cycle 1 day 1.
Patients have a PET-CT scan to check the response after cycle 2. If the scan shows a response and patients are still suitable for CAR-T cell therapy, patients will proceed to receive planned CAR-T therapy and will not receive further Glofit-Pola in Part 1. If not, patients can receive 4 more cycles of glofitamab and polatuzumab vedotin, and then 6 cycles of glofitamab.
干预措施: Obinutuzumab (Drug)
Part 2
Patients whose large B-cell lymphoma has progressed/not responded after standard CAR-T cell therapy.
All patients receive 6 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola), and then 6 cycles of glofitamab alone. Obinutuzumab pre-treatment is given on cycle 1 day 1.
干预措施: Glofitamab (Drug)
Part 2
Patients whose large B-cell lymphoma has progressed/not responded after standard CAR-T cell therapy.
All patients receive 6 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola), and then 6 cycles of glofitamab alone. Obinutuzumab pre-treatment is given on cycle 1 day 1.
干预措施: Polatuzumab vedotin (Drug)
Part 2
Patients whose large B-cell lymphoma has progressed/not responded after standard CAR-T cell therapy.
All patients receive 6 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola), and then 6 cycles of glofitamab alone. Obinutuzumab pre-treatment is given on cycle 1 day 1.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Part 1: Overall Response Rate (ORR) to Pola-Glofit as bridging prior to CAR-T cell infusion
时间窗: At Cycle 2 Day 14-19 (or earlier) (each cycle is 21 days)
To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with r/r LBCL. ORR i.e. the proportion of patients achieving response (Complete Metabolic Response or Partial Metabolic Response) after Pola-Glofit bridging but prior to CAR-T cell infusion, assessed by central review as per 2014 Lugano Classification. This will be presented as a rate with a 70% confidence interval.
Part 2: Progression Free Survival (PFS) at 6 months
时间窗: From the date of registration at Part 2 until the date of first disease progression or death, whichever comes first, assessed up to 4 years
To determine the efficacy of Pola-Glofit in patients with LBCL who have failed to achieve CMR, or progressed after CAR-T cell therapy. PFS at 6 months will be analysed using Kaplan-Meier survival analysis, with the rate at 6 months (with 70% CI) presented. The median (if reached) and plot will also be given.
次要结局
- Part 1: Complete Metabolic Response (CMR) rate to Pola-Glofit as bridging prior to CAR-T cell infusion(At Cycle 2 Day 14-19 of bridging treatment (each cycle is 21 days))
- Part 1: CAR-T associated toxicity post Pola-Glofit bridging following CAR-T therapy(Between Day 0 and Day 28 following CAR-T therapy)
- Part 1: Response rate post CAR-T for all infused patients(From CAR-T infusion until 6 months post CAR-T therapy)
- Part 1: Safety and toxicity of Pola-Glofit as bridging therapy(From registration and during Part 1 bridging treatment, until end of post-treatment safety reporting window (up to six months after last dose of obinutuzumab, plus a further 35 days after last dose of polatuzumab vedotin or last dose of glofitamab))
- Part 2: Complete Metabolic Response (CMR) rate to Pola-Glofit/Glofitamab at any point(From the date of registration until up to 4 years)
- Part 2: Overall Survival (OS)(From the date of registration for Part 2 until the date of death, assessed up to 4 years.)
- Part 1: Overall Survival (OS) and Progression Free Survival (PFS)(From the date of registration at Part 1 until the date of disease progression or death (PFS), or death (OS). This will be assessed from the date of registration until up to 4 years.)
- Part 2: Duration of Complete Response (DoCR)(From the date of first complete metabolic response (CMR) until disease progression, assessed up to 4 years.)
- Part 2: Non-Relapse Mortality (NRM)(NRM will be measured from the date of registration until the date of NRM. This will be assessed from the date of registration until up to 4 years. NRM rates will be presented at 6 months and 1 year.)
- Part 1: Duration of Response (DoR) and Duration of Complete Response (DoCR) for Pola-Glofit and CAR-T(From the date of first response until disease progression. This will be assessed from the date of registration until up to 4 years.)
- Part 2: Response rate for patients who received Pola-Glofit bridging versus those who have not(From the date of registration until Cycle 5 (approximately 12 weeks. Each cycle is 21 days).)
- Part 2: Safety and toxicity of Pola-Glofit post CAR-T therapy(Throughout Part 2 treatment until end of post-treatment safety reporting window (up to six months after last dose of obinutuzumab, plus a further 35 days after last dose of polatuzumab vedotin or last dose of glofitamab))
- Part 2: Duration of Response (DoR)(From the date of first response until disease progression, assessed up to 4 years.)
- Part 1: Non-Relapse Mortality (NRM)(From the date of registration until the date of NRM. This will be assessed from the date of registration until up to 4 years.)
- Part 2: Progression Free Survival (PFS) (at 12 months)(PSF will be measured from the date of registration at Part 2 until the date of disease progression. This will be assessed from the date of registration until up to 4 years. The median rate at 12 months will be presented.)