The Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin s Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Phase 1b adverse events
研究概览
简要总结
Despite the progress in the therapy, Hodgkin's Lymphoma (HL) remains fatal for more than 15% of patients. Even in patients who are cured, the morbidity of therapy is substantial and long-lasting. New therapeutic agents are required therefore not only to further reduce mortality but also to alleviate morbidity.
The majority of HL express the CD30 antigens. CD30 expression is routinely used for the diagnosis of HL. Preclinical observations support CD30 as a viable target of CAR-T therapy. This phase Ib/II study was conducted based on these observations.
The purpose of this study is to determine the tolerability of ATLCAR.CD30.CCR4 cells in subjects with Hodgkin's Lymphoma and identify a recommended dose for further.
This is a single-center, open-label phase Ib/II trial that uses a 3+3 design to identify a recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells in Hodgkin's Lymphoma. The phase II portion is designed to determine the PFS of ATLCAR.CD30.CCR4 in Hodgkin's Lymphoma.
Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments.
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
- •During the period of cell procurement and lymphodepletion, subjects will be eligible to receive standard-of-care therapy e.g., chemotherapy or radiation therapy to stabilize their disease if the treating physician feels it is in the subject's best interests. Eligibility must be maintained up until the subject is procured, receives lymphodepletion, or receives treatment for the subject to be considered eligible to proceed with the specific phase of the study.
- •Inclusion Criteria:
- •Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study. As these criteria are unchanging they will be evaluated at the time of initial enrollment and not continuously throughout the study.
- •Written informed consent and HIPAA authorization for release of personal health information explained to, understood by, and signed by the subject or legally authorized representative.
- •Age ≥ 18 years at the time of consent.
- •Karnofsky score of > 60%
- •The subject must have a diagnosis of Classical Hodgkin Lymphoma according to World Health Organization criteria.
排除标准
- •Subjects had major surgery within 28 days.
- •Subject received investigational agents or tumor vaccines within 3 weeks.
- •Subject received chemotherapy or radiation therapy within the previous 3 weeks.
研究组 & 干预措施
ATLCAR.CD30
Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments
干预措施: Chemotherapy (Drug)
ATLCAR.CD30
Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments
干预措施: Cell infusion (Biological)
结局指标
主要结局
Phase 1b adverse events
时间窗: Up to 6 weeks
Toxicity will be graded as the number of participants with adverse events (AE) related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to CAR.B7-H3T cell product administration.
Phase 1b Toxicity Cytokine Release Syndrome (CRS)
时间窗: Up to 6 weeks
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death
Phase 1b Toxicity Immune effector cell-associated neurotoxicity syndrome (ICANS)
时间窗: Up to 6 weeks
Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Phase II Median Progression Free Survival (PFS)
时间窗: Up to 6 months
Median PFS will be measured from the first day of lymphodepletion chemotherapy prior to ATLCAR.CD30.CCR4 cell infusion to progression (as defined by Lugano Criteria or death. Complete: Complete metabolic response on Positron emission tomography (PET) or the largest transverse diameter (LDi) of target nodes/masses ≤ 1.5 cm and no extra lymphatic disease on Computerized Tomography (CT). Partial: reduced uptake compared with baseline and residual mass(es) on PET and ≥50% decrease in the sum of the products of diameters (SPD) of nodes and extranodal sites on CT. No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD, measurable nodes and extranodal sites; no criteria for the progressive disease are met on CT. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new focus on PET, LDi\>1.5 cm or by ≥ 50% from nadir.
次要结局
- Phase Ib Dose Limiting Toxicity(Up to 6 weeks)
- Overall Survival (OS)(Up to 6 months)
- Duration of Response (DOR)(Up to 6 months)