Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101
This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of ALA-101, an allogeneic, off-the-shelf CD19-directed CAR-iNKT cell therapy, in patients with CD19-positive non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL). The dose-escalation phase will assess safety and determine the maximum tolerated dose (MTD). The dose-expansion/backfill phase will further evaluate safety and preliminary efficacy and establish the recommended Phase 2 dose (RP2D). Study participation includes screening, lymphodepletion, treatment, and follow-up periods. An end-of-study visit will occur at Month 24, after which participants will enter a long-term follow-up study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide
St. Vincent's Hospital
Sydney, New South Wales, Australia
Mater Misericordiae Ltd (MML)
Brisbane, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
To evaluate the safety and tolerability of ALA-101 in adult participants with CD19+ NonHodgkin Lymphoma (NHL) and CD19+ leukemia
Incidence, type and severity of treatment emergent and treatment-related adverse events (AEs) and Incidence and nature of dose-limiting toxicities (DLTs)
Time frame: 2 years
To determine the maximum tolerated dose (MTD) and appropriate recommended Phase 2 dose (RP2D) for progression into next stages of clinical studies in adult participants with CD19+ NHL and/or CD19+ leukemia.
Determination of MTD using isotonic regression and Determination of RP2D considering both the MTD and totality of safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) data collected.
Time frame: 2 years
To evaluate the preliminary efficacy of ALA-101 in adult participants with CD19+ NHL and/or CD19+ leukemia
Overall Response Rate (ORR)
Time frame: 2 years
To characterize the PK profile of ALA-101
Levels of ALA-101 in blood will be assessed using digital polymerase chain reaction (dPCR). Where data permits, endpoints to be evaluated include (but are not limited to): o Maximum observed Peak Plasma Concentration (Cmax)
Time frame: 1 year
To evaluate the immunogenicity of ALA-101
Incidence of anti-ALA-101 antibodies following ALA-101 administration.
Time frame: 2 years
To characterize the PK profile of ALA-101
Levels of ALA-101 in blood will be assessed using digital polymerase chain reaction (dPCR). Where data permits, endpoints to be evaluated include (but are not limited to): Area under the plasma concentration versus time curve (AUC)
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Epworth HealthCare
Richmond, Victoria, Australia
Time frame: 1 Year