Multicenter Phase II Study of Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma
概览
- 阶段
- 2 期
- 干预措施
- Pegfilgrastim
- 疾病 / 适应症
- Diffuse Large B Cell Lymphoma (DLBCL)
- 发起方
- Medical College of Wisconsin
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Complete Response
- 状态
- 尚未招募
- 最后更新
- 昨天
概览
简要总结
This single-arm, interventional phase 2 study is designed to evaluate whether the inclusion of mosunetuzumab subcutaneous and polatuzumab vedotin (Mosun-Pola) to a split-dose CHP chemotherapy backbone will improve outcomes for elderly patients with a new diagnosis of diffuse large B-cell lymphoma.
详细描述
This trial combines two novel agents, mosunetuzumab subcutatneous and polatuzumab vedotin (Mosun-Pola), with cytotoxic chemotherapy while allowing de-escalation in rapidly responding patients. After completing the first two cycles of Mosun-Pola-SD-CHP therapy, subjects will undergo an interim response assessment with positron emission tomography (PET) / computed tomography (CT) and minimal residual disease (MRD) testing (ClonoSEQ; Adaptive Biotechnology) prior to Cycle 3A. Patients who are interim PET-negative and MRD-negative will be placed on an abbreviated treatment regimen, where they will receive Mosun-Pola-SD-CHP therapy for only four cycles.
研究者
Nirav Shah
Professor
Medical College of Wisconsin
入排标准
入选标准
- •Patients aged 70-74 who are determined to be unfit or frail by the Cumulative Illness Rating Scale-Geriatric (CIRS-G) score with 5-8 comorbid conditions scored 2 or more than 1 comorbidity scored 3-4 are allowed.
- •Newly diagnosed, untreated, biopsy-proven CD20 positive diffuse large B-cell lymphoma (DLBCL) (including high-grade B-cell lymphoma and T-cell/histiocyte-rich large B-cell lymphoma). Patients with discordant bone marrow (i.e., involved by low-grade/indolent non-Hodgkin lymphoma) are eligible. Patients with transformed DLBCL from underlying low-grade disease are eligible. Patients with composite DLBCL and concurrent low-grade lymphoma are eligible. Patients with prior treatment for low-grade NHL with non-anthracycline based regimens are eligible.
- •a. Short-course prednisone or equivalent steroid for symptom management is allowable for up to seven days.
- •Measurable disease by positron emission tomography (PET) / computed tomography (CT) using the Lugano criteria (lymph node \>1.5 cm or extranodal site \>1.0 cm).
- •Adequate biospecimen sample that meets current Adaptive Clonality ID Test specimen requirements for DLBCL.
- •a. Note: the preferred ID specimen type is a formalin-fixed paraffin-embedded (FFPE) lymph node biopsy, either FFPE slides or scrolls, targeting 40 microns of material.
- •Left ventricular ejection fraction ≥50% by echocardiography or multigated acquisition (MUGA) scan.
- •Karnofsky Performance Score ≥50 or Eastern Cooperative Oncology Group (ECOG) scan 0-
- •Ann Arbor Stage II bulky, III, or IV disease.
- •Minimum life expectancy greater than 3 months (should be explicitly documented by the enrolling investigator).
排除标准
- •Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy.
- •Current Grade \>1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease.
- •Prior allogeneic or autologous stem cell transplant.
- •Prior solid organ transplant.
- •Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
- •Known or suspected chronic active Epstein-Barr Virus (EBV) infection.
- •History of progressive multifocal leukoencephalopathy (PML).
- •Current or within 6 months of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
- •Patients with SARS-CoV-2 antigen or PCR testing positivity within 30 days prior to Cycle 1 Day
- •a. Any patient with documented SARS-CoV-2 infection within 6 months prior to planned Cycle 1 Day 1 must have no persistent respiratory symptoms, no evidence of residual sequelae, and have a negative PCR test for SARS-CoV-
研究组 & 干预措施
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Pegfilgrastim
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Polatuzumab Vedotin
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Mosunetuzumab
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Cyclophosphamide
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Prednisone
Mosum-Pola-SD-CHP
Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC
干预措施: Doxorubicin
结局指标
主要结局
Complete Response
时间窗: Up to six months.
This is defined as the number of subjects achieving a complete response at the end of treatment using the Lugano criteria.
次要结局
- Partial Response(Up to six months)
- Duration of Response(Up to 60 months)
- Overall Survival(2 years)
- Eligibility for full therapy(56 days)
- Adverse Events(Up to 7 months)
- Study therapy completion(Up to 6 months)
- Eligibility for abbreviated therapy(56 days)
- CRS or ICANS(28 days)
- Minimal residual disease at Cycle 3(56 days)
- Minimal residual disease at end of study treatment(Up to six monts)