A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501A, an Anti-CD19 Allogeneic CAR T Cell Therapy, and ALLO-647, an Anti-CD52 Monoclonal Antibody, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma (LBCL)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 29
- 主要终点
- Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A
研究概览
简要总结
This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.
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
- •For subjects with LBCL:
- •Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017
- •At least 1 measurable lesion at time of enrollment
- •Relapsed or refractory disease after at least 2 lines of chemotherapy
- •Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening (Note: Only applicable for Phase 2)
- •For subjects with CLL/SLL:
- •Diagnosis of CLL/SLL
- •Relapsed/refractory disease
- •Subjects relapsed/refractory to BTKi therapy and high-risk disease
- •Subjects relapsed/refractory with 2 or more lines of therapy including BTKi and BCL-2 inhibitor (venetoclax)
- •At least 1 measurable lesion at time of enrollment
- •For all subjects:
- •Male or female subjects ≥18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Adequate hematological, renal, and liver function
排除标准
- •Active central nervous system (CNS) involvement by malignancy
- •Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy
- •Any other active malignancies that required systemic treatment within 3 years prior to enrollment
- •Radiation therapy within 2 weeks prior to ALLO-647
- •Prior irradiation to >25% of the bone marrow
- •Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening (Note: Only applicable for Phase 2).
- •Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
- •Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647
研究组 & 干预措施
ALLO-501A, ALLO-647
干预措施: ALLO-501A (Genetic)
ALLO-501A, ALLO-647
干预措施: ALLO-647 (Biological)
ALLO-501A, ALLO-647
干预措施: Fludarabine (Drug)
ALLO-501A, ALLO-647
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A
时间窗: 28 days
Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion
Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A
时间窗: 33 days
DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion
Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest
时间窗: Up to 60 months
Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC)
时间窗: Up to 60 months
ORR defined as assessment of CR and PR using Lugano classification criteria 2014
次要结局
- Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator(Up to 60 months)
- Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator(Up to 60 months)
- Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count(Up to 9 months)
- Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647(Up to 60 months)
- Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator(Up to 60 months)
- Phase 1a, 1b, and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator(Up to 60 months)
- Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery(Up to 9 months)
- Phase 1a, 1b, and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model(Up to 9 months)
- Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®(Up to 9 months)
- Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647(Up to 9 months)
- Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator(Up to 60 months)
- Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)(Up to 9 months)
- Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)(Up to 9 months)
- Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts(Up to 9 months)
- Phase 1a, 1b, and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A(Up to 60 months)
- Phase 1a, 1b, and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647(Up to 60 months)
- Phase 1a, 1b, and 2: Overall Survival (OS)(Up to 60 months)
- Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)(Up to 9 months)
- Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)(Up to 9 months)