2022-502305-15-00招募中2 期
Open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART22 (allogeneic engineered T-cells expressing Anti-CD22 Chimeric Antigen Receptor) in patients with relapsed or refractory CD22+ B-cell Acute Lymphoblastic Leukemia (B-ALL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Cellectis
- 入组人数
- 40
- 试验地点
- 11
- 主要终点
- Dose escalation Phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
研究概览
简要总结
For the Dose-escalation: -To assess the safety and tolerability of UCART22 and determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of UCART22 in patients with R/R BALL.
For the Dose-Expansion: -To confirm the MTD and/or RP2D in patients with R/R B-ALL who have failed a CD19 directed therapy.
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 18-64 Years, 0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Age: a.Dose Escalation phase: Patient aged ≥15 years and ≤70 years; b.Dose Expansion phase: Patient aged ≥12 and ≤70 years
- •Diagnosis and Prior Therapy: a.Dose Escalation phase: Diagnosed with R/R B-ALL; prior therapy must include at least one standard chemotherapy regimen and at least one salvage regimen. There must be no available alternative curative therapies and patients must be ineligible for allogeneic hematopoietic stem cell transplantation (HSCT), have refused HSCT, recurred after HSCT, or have active disease that prohibits HSCT at the time of enrollment. b.Dose Expansion phase: Diagnosed with R/R B-ALL; prior therapy must include at least one standard chemotherapy regimen and at least one salvage regimen, and must have included a CD19 targeted treatment. There must be no available alternative curative therapies and patients must be ineligible for allogeneic hematopoietic stem cell transplantation (HSCT), have refused HSCT, recurred after HSCT, or have active disease that prohibits HSCT at the time of enrollment
- •Disease burden: a.Dose Escalation phase: Patients must have measurable or evaluable disease in the bone marrow of at least 0.01% blasts or non-CNS extramedullary disease at the time of enrollment; b.Dose Expansion phase: Patients must have measurable or evaluable disease in the bone marrow of at least 5% blasts at the time of enrollment
- •CD22 Expression: a.Dose escalation phase: At least 70% of B-ALL blast cells expressing CD22 by flow cytometry performed as per standard practice; b.Dose expansion phase: At least 70% of B-ALL blast cells must express CD22 by flow cytometry performed as per standard practice
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 for subjects ≥ 18 years; Lansky/Karnofsky score ≥ 70 for subjects < 18 years
- •Adequate organ function, including renal and hepatic function based on the last assessment performed within the Screening Period, defined as: i)Creatinine clearance ≥60 mL/min (assessed as glomerular filtration rate using the Cockcroft-Gault formula); ii)Alanine aminotransferase and aspartate aminotransferase 3×upper limit of normal (ULN) or ≤5×ULN if deemed to be elevated due to leukemic involvement; iii)Total bilirubin 2×ULN or ≤3×ULN if deemed to be elevated due to leukemic involvement; iv)Left ventricular ejection fraction ≥50%
- •Women of childbearing potential must have a negative, highly sensitive serum pregnancy test performed within 7 days prior to enrollment
排除标准
- •Prior CAR T cellular therapy or investigational cellular therapy within 60 days prior to enrollment
- •Allogeneic HSCT within 90 days prior to enrollment
- •Donor lymphocyte infusion within 6 weeks prior to enrollment
- •Active, acute or chronic graft-versus-host disease (GvHD). Patients should be off all immunosuppression for 6 weeks prior to enrollment
- •Radioimmunotherapy or radiotherapy within 8 weeks
- •Hyperleukocytosis (≥10,000 blasts/μL) or rapidly progressive disease
- •Patients with radiologically-detected CNS leukemia or CNS-3 disease
- •Presence of an active and clinically relevant CNS disorder
- •Isolated extramedullary relapse (i.e., testicular, CNS)
- •Known infection with human immunodeficiency virus or human T-cell leukemia/lymphoma virus type 1 or active hepatitis B or active hepatitis C
- •Any known uncontrolled cardiovascular disease in the previous 6 months before enrollment
- •Prior CD22 directed CAR T cell therapy
- •History of severe recurrent viral infections or active bacterial, fungal, or viral infection not controlled by adequate treatment at enrollment
- •Abnormal findings and/or clinically significant Grade ≥3 non hematological toxicity that might jeopardize the patient's safety
- •Evidence of another uncontrolled malignancy within 2 years prior to Screening
- •Active macrophage activation syndrome (MAS)
- •For a patient intended to receive alemtuzumab as part of their lymphodepletion regimen (Arm FCA): i)History of hypersensitivity to alemtuzumab; or ii)Inability for any reason to receive appropriate anti-infective prophylaxis.
- •Prior monoclonal antibody therapy within 30 days prior to enrollment
- •Use of other investigational products within 5 half-lives or within 14 days prior to enrollment, whichever is longer
- •Use of systemic chemotherapy within 14 days prior to enrollment (except 6 weeks for nitrosoureas)
- •Use of rituximab, other anti-CD20 antibodies known to have the same epitope as rituximab, or anti-CD20 antibodies for which the epitope is unknown within 3 months prior to enrollment
- •Planned treatment with > 20 mg of prednisone or equivalent between Days -7 and +28 of UCART22 infusion
- •Burkitt cell leukemia
- •More than 1 allogeneic HSCT received
结局指标
主要结局
Dose escalation Phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
Dose escalation Phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
Dose Escalation phase: Proportion of patients in each dose level cohort with dose-limiting toxicity during the DLT observation period
Dose Escalation phase: Proportion of patients in each dose level cohort with dose-limiting toxicity during the DLT observation period
Dose expansion phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
Dose expansion phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
次要结局
- Dose Escalation phase: Investigator assessed overall response rate (ORR) [complete response + complete response CR with incomplete hematologic recovery +complete response with partial hematologic recovery [CR+CRi+ CRh]) according to the Response criteria for Acute Lymphoblastic Leukemia (ALL) and Investigator assessed rate of MRD negativity defined as (BM ALL blasts <0.01%) by flow cytometry
- Dose Escalation phase: Investigator assessed rate of minimal residual disease (MRD) negativity (defined as bone marrow (BM) ALL blasts < 0.01%) by flow cytometry
- Dose Escalation phase: Time to Event Endpoints: Progression free survival (PFS); overall survival (OS) and duration of response (DoR)
- Dose Escalation phase: Proportion of patients who achieve adequate response and proceed to hematopoietic stem cell transplant (HSCT)
- Dose Escalation phase: Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion, associated anti-leukemic activity and corresponding host T-cell recovery and CAR+ T-cell expansion
- Dose Escalation phase: Monitoring of anti-CD52 (alemtuzumab) antibodies in serum pre- and post-administration of alemtuzumab
- Dose Escalation phase: Quantitation of alemtuzumab levels in serum post administration
- Dose Escalation phase: Quantitation of T, B, and NK cells and total lymphocytes in periperal blood post administration
- Dose Expansion Phase: Investigator assessed ORR (CR+CRi+CRh) according to the Response criteria for ALL
- Dose Expansion Phase:Time to Event Endpoints: Progression free survival (PFS); overall survival (OS) and duration of response (DoR)
- Dose Expansion phase: Proportion of subjects who achieve adequate response and proceed to hematopoietic stem cell transplant (HSCT) without additional antileukemia therapy
- Dose Expansion phase: MRD negative rate measured on BM by ClonoSeq MRD assay at central laboratory
- Dose Expansion phase:Incidence, nature and severity of adverse events and serious adverse events (SAEs) during the Dose Expansion phase
- Dose Expansion phase: Monitoring of anti-CD52 (alemtuzumab) antibodies in serum pre- and post-administration of alemtuzumab)
- Dose Expansion phase: Quantitation of alemtuzumab levels in serum post administration
- Dose Expansion phase: Quantitation of T, B, and NK cells and total lymphocytes in periperal blood post administration
研究者
clinical trial information desk
Scientific
Cellectis
研究点 (11)
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