Phase 1 Study of Redirected Autologous T Cells Engineered to Contain an Anti-CD19 and Anti-CD20 scFv Coupled to CD3ζ and 4-1BB Signaling Domains in Patients With Relapsed/ Refractory CD19 or CD20 B-cell Acute Lymphoblastic Leukemia
概览
- 阶段
- 1 期
- 干预措施
- CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg)
- 疾病 / 适应症
- Acute Lymphoblastic Leukemia, in Relapse
- 发起方
- Medical College of Wisconsin
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Adverse Events after CAR 20/19-T Cell Infusion.
- 状态
- 终止
- 最后更新
- 3个月前
概览
简要总结
This phase 1 study will evaluate the safety and efficacy of a CAR-T cell therapy directed against two B cell antigens (CD19 CD20) and produced under good manufacturing practice (GMP) conditions using the closed system CliniMACS Prodigy device in B ALL.
详细描述
This is a phase 1, interventional, open label, treatment study designed to evaluate the safety and feasibility of infusion of CAR-20/19-T in subjects with B cell ALL who have relapsed after prior therapies or refractory disease and are not candidates for curative intent standard therapy. There will be two phases of this study. First, a dose escalation phase will determine the safe CAR-20/19-T cell dose in patients B-cell ALL. Once the desired dose has been identified there will be a six-patient dose expansion phase at the specified dose level.
研究者
Julie-An M. Talano
Professor
Medical College of Wisconsin
入排标准
入选标准
- •Diagnosis of B-cell ALL: During the safety phase patients enrolled will be age ≥ 18 to age ≤
- •Once those three patients have passed the 28-day waiting period post infusion, clearance from the FDA will be obtained to enroll pediatric patients. After FDA clearance -Patients must be aged ≥ 1 year and ≤ 70 years. All patients will have relapsed, refractory disease and no available curative options that meet clinical criteria to initiate treatment.
- •Relapsed or refractory B cell ALL defined as one of the following:
- •Primary refractory disease.
- •Relapsed or refractory disease after two or more lines of systemic therapy.
- •Relapsed or refractory disease after allogeneic transplant provided subject is at least 100 days from stem cell transplant at the time of enrollment and off of immunosuppressive medications for at least four weeks prior to enrollment.
- •Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, or cytogenetics, or morphological disease in the bone marrow.
- •Subjects with B-cell ALL must have either CD19 or CD20 positive disease on their most recent bone marrow performed. A minimum of 5% CD19 or CD20 positivity on prior biopsy or bone marrow aspiration (BMA) is required.
- •Subjects with Ph+ ALL are eligible if they have relapsed or refractory disease and have failed at least two tyrosine kinase inhibitors.
- •Absolute cluster of differentiation 3 (CD3)+ T cell count ≥100/mm\^
排除标准
- •Positive beta-human chorionic gonadotropin (HCG) in female of childbearing potential.
- •Subjects with known systemic allergy to bovine or murine products.
- •Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- •History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy defined as \>20 mg of prednisone.
- •Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5 from any previous treatment unless it is felt to be due to underlying disease.
- •Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution.
- •Refusal to participate in the long-term follow-up protocol.
- •Central nervous system (CNS) Abnormalities:
- •Subjects with prior CNS disease that has been effectively treated will be eligible providing treatment was \> four weeks before enrollment and a remission documented within four weeks of planned CAR-T cell infusion. Subjects will be excluded if they have any signs of neurotoxicity at baseline or evidence of chloroma or leukemic infiltrates on MRI.
- •Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 white blood cells (WBCs) per mm\^3 with or without neurological changes, and presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample of CSF with \< 5 WBCs per mm\^3 with neurological changes will be excluded.
研究组 & 干预措施
5 x 10^5 CAR-20/19-T cells/kg
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.
干预措施: CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg)
1 x10^6 CAR-20/19-T cells/kg
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.
干预措施: CAR-20/19-T cells (1 x10^6 CAR-20/19-T cells/kg)
2.5 x10^6 CAR-20/19-T cells/kg
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.
干预措施: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
Dose Expansion Phase
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort. Subjects will receive one of three dose levels. The dose expansion arm will be updated with the appropriate dose in the future based on the escalation results.
干预措施: CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg)
Dose Expansion Phase
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort. Subjects will receive one of three dose levels. The dose expansion arm will be updated with the appropriate dose in the future based on the escalation results.
干预措施: CAR-20/19-T cells (1 x10^6 CAR-20/19-T cells/kg)
Dose Expansion Phase
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort. Subjects will receive one of three dose levels. The dose expansion arm will be updated with the appropriate dose in the future based on the escalation results.
干预措施: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
Dose Expansion Phase
The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort. Subjects will receive one of three dose levels. The dose expansion arm will be updated with the appropriate dose in the future based on the escalation results.
干预措施: CAR-20/19-T cells
结局指标
主要结局
Number of Adverse Events after CAR 20/19-T Cell Infusion.
时间窗: 28 days after infusion
Adverse events will be measured and recorded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Occurrence of adverse events, defined as either CRS related Grade 3/4 toxicity or other NCI CTCAE version 5 non-hematologic ≥ grade 3 signs/symptoms, laboratory toxicities and clinical events that are possibly, probably or definitely related to study treatment at any time from the infusion until day +28 post CAR-T infusion.