NCT07701889尚未招募1 期
A Phase I Trial of Bispecific CD19/CD20-Targeted Chimeric Antigen Receptor (CAR) Modified T Cells With 4-1BB and Mutated CD28 Costimulatory Domains in Patients With Relapsed or Refractory CD19+ Hematologic Malignancies
适应症
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MDT)
研究概览
简要总结
To determine the safety, toxicity, and maximum tolerated dose (MTD) of CD19/CD20 bispecific CAR-T cells with 4-1BB and mutated CD28 costimulatory domains (20-19 Tan BB06z) in patients with relapsed or refractory CD19+ aggressive hematologic malignancies
详细描述
The purpose of this study is to test the safety of 20-19 Tan BB06z CAR T cells in people with different types of relapsed/refractory CD19-positive blood cancer. Different doses of 20-19 Tan BB06z CAR T cells will be tested to find the highest dose that causes few or mild side effects in participants
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for leukapheresis, patients must have an aggressive CD19+ B cell malignancy with relapsed or refractory disease, defined as below.
- •To be eligible for treatment with 20-19 Tan BB06z CAR-T cells, patients must additionally have detectable evidence of residual malignancy at the time of assessment prior to CAR-T cell infusion, regardless of therapy administered following leukapheresis.
- •To be included in this study, participants must meet the following criteria:
- •1. Patients with R/R B-Cell malignancies (see below) which commonly express CD19 and CD
- •Eligible disease subtypes include the following:
- •o DLBCL/HGBL de novo or DLBCL/HGBL transformed from an indolent lymphoma, refractory to front-line chemoimmunotherapy containing an anthracycline and CD20-directed therapy (without achievement of CR).
- •Relapsed or refractory DLBCL/HGBL following 2 or more prior chemoimmunotherapy regimens containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma.
- •Relapse following a single prior chemoimmunotherapy regimen containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and considered ineligible for high dose chemotherapy and autologous stem cell rescue as determined by the investigator.
- •Mantle Cell Lymphoma after 2 lines of therapy. Patients must have previously received chemoimmunotherapy and a prior BTK inhibitor.
- •Secondary CNS Lymphoma after 2 lines of therapy, 1 of which must include an autologous stem cell transplant or deemed ineligible by the investigator.
- •Patients with B cell acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) in lymphoid blast crisis.
- •Patients with Philadelphia chromosome-negative B cell ALL must have been refractory to at least 1 line of multi-agent chemotherapy or relapsed following at least 1 prior multiagent systemic chemotherapy regimen that included induction and consolidation therapy.
- •Patients with Philadelphia chromosome-positive ALL or CML in lymphoid blast crisis must have exhibited persistent disease following therapy with a second- or third-generation tyrosine kinase inhibitor.
- •Burkitt lymphoma refractory to at least 1 line of multi-agent chemotherapy or relapsed following 1 or more lines of multi-agent chemotherapy.
- •Patients must have at least one FDG-avid (PET-avid) measurable lesion.
- •For B-cell ALL and/or CML in lymphoid blast crisis, presence of > 20% lymphoid blasts in the blood or bone marrow, or extramedullary infiltration with FDG-avid (PET-avid) measurable lesion is required.
- •3. Prior CD19-targeted therapies, including CAR-T cell therapy, do not exclude participation. However, CD19 and CD20 expression by immunohistochemical staining or flow cytometry must be confirmed prior to enrollment for patients who have received such therapies.
- •Have the following clinical laboratory values:
- •Adequate renal function defined as;
- •- Adult participants:
- •Creatinine Clearance >30 mL/min (Cockroft-Gault equation)
- •- Pediatric participants: Use age/gender -appropriate creatinine as follows: Age Maximum Plasma Creatinine (mg/dL) Male Female 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- •≥ 16 years 1.7 1.4
- •Direct bilirubin ≤2.0 mg/dL
- •AST and ALT ≤3.0x upper limit of normal (ULN)
- •Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.
- •ECOG performance status 0-1 for adult participants ≥18 years of age. Pediatrics - Lansky/Karnofsky score ≥70: use Karnofsky for participants ≥16 years of age and Lansky for participants <16 years of age (see Appendix A).
- •Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Participants of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
- •9. Participant, or legal representative, must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
排除标准
- •Pregnant or lactating patients.
- •Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan during screening.
- •Patients with active known autoimmune disease requiring systemic T cell suppressive therapy are ineligible.
- •Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T cell suppressive therapy are ineligible.
- •Patients with following cardiac conditions will be excluded:
- •New York Heart Association (NYHA) stage III or IV congestive heart failure
- •Myocardial infarction ≤6 months prior to enrollment
- •Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- •Patients with HIV are ineligible.
- •Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen) are ineligible.
- •Patients with active hepatitis C infection (as manifest by detectable hepatitis C virus RNA by PCR) are ineligible. Patients with detectable antibodies to hepatitis C virus will be screened by PCR for evidence of active infection.
- •Patients with uncontrolled systemic fungal, bacterial, viral or other infection are ineligible.
- •Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.
- •Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.
- •Unwilling or unable to follow protocol requirements.
- •Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study.
结局指标
主要结局
Maximum Tolerated Dose (MDT)
时间窗: up to 2 years
MTD will be established from Dose limiting toxicities after infusion
次要结局
- Overall Survival(Up to 2 years)
- persistence of modified T-cells(Up to 2 years)
- Event Free Survival(UP to 2 years)
研究者
研究点 (1)
Loading locations...
相似试验
尚未招募
1 期
Study Investigating the Safety of Anti-CD19 CAR-T Cells Therapy Produced at Gustave Roussy for Adults With Severe and Refractory Systemic Autoimmune Rheumatic DiseasesRheumatoid Arthritis (RA)Systemic Lupus Erythematosus (SLE)Sjogren's Disease With Dry EyesSystemic Sclerosis (SSc)Idiopathic Inflammatory Myositis (IIM)NCT07544225Gustave Roussy, Cancer Campus, Grand Paris6
招募中
2 期
CD19/CD22 CAR-T as First-line Consolidation in Follicular LymphomaLymphomaNCT07587840Liping Dou20
招募中
2 期
CARLA-M19 : “Prospective non-randomized phase I/II study investigating the safety of CD19 CAR-T cells in patients with refractory/relapsed AML (Acute Myeloïd Leukemia) expressing CD19.”2023-509212-29-01Centre Hospitalier Universitaire De Lille5
招募中
1 期
CD19 CAR T-Cell Therapy for Refractory Systemic Lupus ErythematosusNCT07432334Vinmec Research Institute of Stem Cell and Gene Technology8
尚未招募
1 期
A Clinical Study of Humanized CD19 CAR-T Cells With TLR2 for the Treatment of Adult Patients With Naive B-Cell Acute Lymphoblastic Leukemia/Lymphoma Who Are Intolerant to Intensive ChemotherapyNCT07335094Zhujiang Hospital60