2022-501686-47-00招募中1/2 期
A Phase I/II study to evaluate the feasibility, safety and preliminary efficacy of point-of-care manufactured anti-CD19 CAR T in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Galapagos, Galapagos3 个研究点 分布在 3 个国家目标入组 25 人开始时间: 2022年11月4日最近更新:
试验速览
- 阶段
- 1/2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Phase I: Incidence of (serious) adverse events, including dose-limiting toxicities (DLT)
研究概览
简要总结
The primary objective of the phase I part of the study is to evaluate the safety and preliminary efficacy of BCN-CP01 to determine the RP2D. The primary objective of the phase II part of the study is to evaluate the efficacy of BCN-CP01, as measured by the objective response rate (ORR).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent form
- •Women of childbearing potential and all male subjects must agree to use highly effective methods of contraception (failure rate of < 1% per year when used consistently and correctly) and agree to remain on a highly effective method of contraception from the time of signing the informed consent form until at least 6 months after BCN-CP01 infusion. Subjects must agree to not donate eggs or sperm during this period.
- •Age ≥ 18 years
- •Histologically confirmed diagnosis of CD19+ CLL or SLL with an indication for therapy according to iwCLL criteria, Richter's transformation is allowed
- •Documented relapsed or refractory disease after at least 2 prior lines of therapy: 1) Subjects must have been exposed (or be intolerant/ineligible or did not consent) to Bruton tyrosine kinase (BTK)-inhibitors (e.g. ibrutinib, acalabrutinib), BCL2-inhibitors (e.g. venetoclax) and/or PI3K inhibitors (e.g. idelalisib, duvelisib); 2) Richter's patients who failed a BTK-inhibitor are eligible regardless of number of prior lines of therapy received
- •Measurable disease according to iwCLL
- •ECOG performance status of 0 or 1
- •Adequate bone marrow function defined as: 1) Absolute neutrophil count (ANC) ≥ 500/μL or ≥ 0.5 × 109/L (without G-CSF support within 7 days of the laboratory test or pegylated G-CSF support within 14 days of the laboratory test); 2) Platelet count ≥ 50,000/μL or ≥ 50 x 109/L (without prior platelet transfusion within 7 days before the laboratory test); 3) Absolute lymphocyte count ≥ 300/μL or ≥ 0.3 × 109/L; 3) CD3+ count ≥ 150/μL or ≥ 0.15 × 109/L
- •Adequate renal, hepatic and pulmonary function defined as: 1) Serum albumin ≥ 3.4 g/dL; 2) Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min; 3) Aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); 4) Alanine aminotransferase (ALT) ≤ 3 × ULN; 5) Total bilirubin ≤ 2 x ULN, except in subjects with Gilbert's syndrome; 6) No clinically significant pleural effusion; 7) Baseline oxygen saturation > 92% on room air
- •Women of childbearing potential must have a negative serum pregnancy test at screening and prior to the first dose of cyclophosphamide and fludarabine
排除标准
- •Prior treatment: • Any anti-CD19 targeted therapy • Salvage systemic therapy within 2 weeks or 5 half-lives (whichever is shorter) prior to leukapheresis • Allogeneic stem cell transplant within 6 months before leukapheresis. Subjects who received an allogeneic transplant must have stopped all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Subjects with active significant (overall Grade ≥ II, Seattle criteria) active graft-versus-host disease (GVHD) or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids are excluded. • Corticosteroid therapy at a pharmacologic dose (> 10 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs are not allowed for 7 days prior to leukapheresis and < 72 hours prior to BCN-CP01 infusion (if restarted)
- •History of malignancy other than lymphoma, except: a. non-melanoma skin cancer b. Carcinoma in situ (e.g. skin, cervix, bladder, breast) and disease free for at least 3 years prior to screening c. Superficial bladder cancer d. Asymptomatic low-grade or curatively treated localized prostate cancer for which watch-and-wait approach is standard of care e. Any other cancer that has been in remission for ≥3 years prior to enrollment
- •History of BTK-associated side effects (e.g. symptomatic atrial fibrillation) or co-morbidities (e.g. oral anticoagulation, severe hemophilia, or von Willebrand’s disease, etc.) that would prevent the patient from taking ibrutinib during the screening phase
- •Contraindication for Fludarabine or Cyclophosphamide
- •Known allergy or hypersensitivity to tocilizumab
- •Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less
- •Active CNS involvement (with neurological changes) by disease under study, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was > 4 weeks before screening
- •Clinically significant cardiac disease within 12 months of screening such as: • Impaired cardiac function (LVEF < 45%) as assessed by echocardiogram performed ≤ 4 weeks prior to screening • Evidence of pericardial effusion as determined by echocardiogram • New York Heart Association Class III or IV congestive heart failure • Clinically significant arrhythmias
- •Primary immunodeficiency
- •Stroke or seizure within 6 months of screening
- •History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within 2 years prior to screening
- •Infection with HIV, hepatitis B or hepatitis C virus. A history of hepatitis B or C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- •Uncontrolled infection or infection requiring antimicrobials for management, at screening
- •Vaccinated with live attenuated vaccine ≤ 4 weeks prior to leukapheresis
- •Pregnant or nursing women, or planning to become pregnant within 12 months after BCN-CP01 infusion
- •No major surgery ≤2 weeks prior to leukapheresis
- •In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
结局指标
主要结局
Phase I: Incidence of (serious) adverse events, including dose-limiting toxicities (DLT)
Phase I: Incidence of (serious) adverse events, including dose-limiting toxicities (DLT)
Phase II: Best objective response rate per iwCLL response criteria (Lugano classification for Richter's transformation)
Phase II: Best objective response rate per iwCLL response criteria (Lugano classification for Richter's transformation)
次要结局
未报告次要终点
研究者
Marte Liefaard
Scientific
Galapagos
研究点 (3)
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