A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
概览
- 阶段
- 1 期
- 干预措施
- Chimeric Antigen Receptor T-Cell Therapy
- 疾病 / 适应症
- Recurrent B-Cell Non-Hodgkin Lymphoma
- 发起方
- Fred Hutchinson Cancer Center
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Dose-limiting Toxicities (DLT) Rate
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
The purpose of this research is to find the best dose of genetically modified T-cells, to study the safety of this treatment, and to see how well it works in treating patients with B cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous treatment (refractory).
详细描述
OUTLINE: This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy. Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide intravenously (IV). Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes. Patients will be actively participating in the study for approximately 15 months. The total time includes the time for the T cells to be made, the T cell infusion, and for approximately 12 months after the T cell infusion is given. After completion of study treatment, patients are followed up for a minimum of 15 years.
研究者
Mazyar Shadman
Associate Professor
Fred Hutchinson Cancer Center
入排标准
入选标准
- •Patients must have B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Eligible lymphoma subtypes include (but not limited to): mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chronic lymphoid leukemia \[CLL\]), or diffuse large B cell lymphoma that has relapsed after a response to at least one prior therapy regimen or is refractory to prior therapy; patients with mantle cell lymphoma must have previously been treated with a Bruton tyrosine kinase (BTK) inhibitor and have either had disease progression, intolerance, or exposure to the drug for at least 3 months; patients with CLL/SLL are eligible if they had disease progression or intolerance to BTKis and/or a BCL-2 inhibitors; they are also required to have been treated with the other agent for at least 3 months (i.e. patients with progression/intolerance to BTKi need to be treated with a BCL-2 inhibitor for at least 3 months, and patients with progression/intolerance to BCL-2 inhibitor need at least 3 months of exposure to a BTKi); patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:
- •Biopsy-proven refractory disease after a frontline regimen containing both an anthracycline and rituximab or other anti-CD20 antibody (i.e. "primary refractory"), where any disease recurring within 6 months of completion of the regimen is considered refractory
- •Relapsed or refractory disease after at least one of the following:
- •At least 2 lines of therapy (including at least one with an anthracycline and anti-CD20 antibody)
- •Autologous stem cell transplant
- •Allogeneic stem cell transplant
- •Patients with large cell lymphoma transformed from indolent lymphomas are eligible if previously treated with anthracycline containing regimen for either the indolent or large cell histology
- •Patients with central nervous system (CNS) lymphoma need to meet one of the following criteria:
- •Primary CNS lymphoma:
- •Progressive disease after 3 cycles or an inadequate response after at least 4 cycles of a high-dose methotrexate (MTX) containing regimen in the opinion of the treating physician, OR
排除标准
- •Active autoimmune disease requiring systemic immunosuppressive therapy
- •Patients requiring corticosteroid therapy at a dose of 15 mg or more per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable
- •Patients who are human immunodeficiency virus (HIV) seropositive
- •Women who are pregnant or breastfeeding
- •Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (\> New York Heart Association \[NYHA\] class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia
- •History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
- •History or presence of clinically relevant non-lymphoma central nervous system pathology, including seizures that are uncontrolled on anticonvulsant therapy (\>= 1 seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, or psychosis
- •Treatment with any investigational agent on a different clinical trial within 4 weeks prior to enrollment, unless the patient is documented to be unresponsive to the therapy and at least 3 half-lives have elapsed prior to enrollment
- •Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks before enrollment
- •Previous treatment with CD19-targeted CAR T cells that has resulted in ongoing B cell aplasia at the time of enrollment; patients that demonstrate recovery of normal B cells (\>= 20 B cells/ul) by flow cytometry at any point 28 days or later after CD19 CAR T cell infusion will be considered to have functional loss of CD19 CAR T cells and are potentially eligible
研究组 & 干预措施
Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
干预措施: Chimeric Antigen Receptor T-Cell Therapy
Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
干预措施: Leukapheresis
Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
干预措施: Cyclophosphamide
Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
干预措施: Laboratory Biomarker Analysis
Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
干预措施: Fludarabine Phosphate
结局指标
主要结局
Dose-limiting Toxicities (DLT) Rate
时间窗: Up to 28 days
Will be graded by Common Terminology Criteria for Adverse Events version 4.0. Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Outcome reported as count of participants in each arm who experienced a DLT.
次要结局
- Complete Remission(Up to 15 years)
- Progression-free Survival (PFS)(Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years)
- Overall Survival (OS)(Duration from study enrollment to death due to any cause, assessed up to 15 years)
- Incidence of Adverse Events(Up to 15 years)