Study of ALA-101 in Patients With CD19 Positive Non-Hodgkin Lymphoma and Leukemia.

A Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101, Allogeneic, Off-the-shelf, CD19-directed CAR-iNKT Cells in Patients With CD19+ Non-Hodgkin Lymphoma and Leukemia

Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101

Study Overview

• Status: Not yet recruiting
• Conditions: Non Hodgkin Lymphoma (NHL); Leukaemia
• Intervention / Treatment: Drug: ALA-101

Detailed Description

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
• Enrollment (Estimated): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
      • Contact: Dr Danielle Blunt; Phone Number: 08 7074 0000; Email: Health.CALHNClinicalTrials@sa.gov.au
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
      • Contact: Dr Salvatore Fiorenza; Phone Number: (03) 9903 0122; Email: acbd@monash.edu
    • Richmond, Victoria, Australia, 3121
      • Epworth Healthcare
      • Contact: Dr Sumi Ratnasingam; Phone Number: 03 9426 0555; Email: EHBloodCancer@epworth.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Over 18 years old
• Confirmed Diagnoses of Confirmed diagnosis of CD19+ non-Hodgkins lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphatic Leukemia or Hairy Cell Leukemia
• Life Expectancy greater than 3 months
• Adequate Hepatic and Renal Function
• Adequate Bone Marrow Function
• Adequate ECG Vales
• Agree to use appropriate contraception to avoid becoming pregnant for up to 12 months post treatment and agree not to donate sperm or ova for 12 months post treatment

Exclusion Criteria:

• Prior anti-CD1d monoclonal antibody treatment
• Prior allogeneic stem cell transplant except where the participant is greater than 100 days and does not have Graft Versus Host Disease (uncontrolled)
• Prior Organ Transplant
• Previous Malignancy in last 3 years that's active or been treated.
• Current central nervous system involvement by lymphoma or leukaemia
• Evidence of Cardiac Dysfunction
• Active Autoimmune disease requiring systemic immunosuppressive therapy within the past 6 months.
• Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
• History of Graft Vs Host Disease Grade 2 to 4
• No active Graft Vs Host Disease following a minimum of 3 months withdrawal from all Graft Vs Host Disease treatments
• Must not have received systemic anti-cancer therapy for the underlying malignancy within 6 weeks prior to the start of conditioning chemotherapy on Day -6.
• Participants that have received autologous or allogenic CAR-T cell therapy within 3 months prior to commencing screening.
• Use of systemic corticosteroids within 15 days of commencement of conditioning chemotherapy on Day -6 or other immunosuppressive drugs within 30 days
• Recent major surgery (within 4 weeks prior to commencement of conditioning chemotherapy on Day -6) or planned major surgery within 8 weeks following ALA-101 infusion on Day 1.
• Active infection requiring intravenous antibiotic, antifungal, or antiviral medication or hospital admission within 10 days prior to commencement of conditioning chemotherapy on Day -6
• Severe (e.g., severe chronic obstructive pulmonary disease, severe Parkinson's disease) or poorly controlled (e.g., hypertension, diabetes, active inflammatory bowel disease) medical condition.
• Vaccinated with a live vaccine within 28 days prior to commencement of conditioning chemotherapy on Day -6 or planned live vaccination within 6 months following ALA-101 infusion.

Additional criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Dose Level 1; 50 × 10^6 CAR+ iNKT cells (starting dose level)	Drug: ALA-101; Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide
Experimental: Treatment Dose Level -1; Dose level -1: 20 × 10^6 CAR+ iNKT cells (in case of DLTs on Dose Level 1)	Drug: ALA-101; Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide
Experimental: Treatment Dose Level 2; 150 × 10^6 CAR+ iNKT cells	Drug: ALA-101; Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide
Experimental: Treatment Dose Level 3; 300 × 10^6 CAR+ iNKT cells	Drug: ALA-101; Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide
Experimental: Treatment Dose Level 4; 500 × 10^6 CAR+ iNKT cells	Drug: ALA-101; Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years
To evaluate the preliminary efficacy of ALA-101 in adult participants with CD19+ NHL and/or CD19+ leukemia	Overall Response Rate (ORR)	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)	1 year
To evaluate the immunogenicity of ALA-101	Incidence of anti-ALA-101 antibodies following ALA-101 administration.	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)	1 Year

Collaborators and Investigators

• Sponsor: Arovella Therapeutics Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): August 30, 2030

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lymphoma; Leukemia; iNKT; C19+; CART T CELL; CAR iNKT
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ALA-101-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No