Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2)

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)

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.

Inclusion Criteria:

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

Exclusion Criteria:

• 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