A Study to Investigate the Safety and Preliminary Efficacy of ALLO-329, an Allogeneic CAR T-cell Therapy, in Adults With Autoimmune Disease

Official title

A Phase 1 Study Evaluating the Safety and Preliminary Efficacy of ALLO-329, a Dual Anti-CD19/Anti-CD70 Allogeneic CAR T Cell Product in Autoimmune Disease

Overview

This is a first-in-human, single-arm, open-label study evaluating the safety, tolerability, and preliminary efficacy of ALLO-329 in adults with autoimmune diseases: systemic lupus erythematosus (SLE) with and without renal involvement, idiopathic inflammatory myopathy (IIM), and systemic sclerosis (SSc).The purpose of this trial is to evaluate the safety and tolerability of ALLO-329, an allogeneic anti-CD19, anti-CD70 dual chimeric antigen receptor (CAR) T cell therapy, in adults with autoimmune disorders, provide initial evidence of biological activity and clinical response to the treatment and determine the recommended Phase 2 regimen (RP2R).

Interventions

• Genetic ALLO-329
  An allogeneic CAR T cell therapy targeting CD19 and CD70
• Drug Cyclophosphamide
  Chemotherapy for lymphodepletion
• Drug Fludarabine
  Chemotherapy for lymphodepletion

Primary outcome measures

• Incidence of Dose Limiting toxicities (DLTs) and Other Safety Parameters [Time frame: Up to 60 months]

Secondary outcome measures (8)

• Disease Response to Treatment - Systemic Lupus Erythematosus [Time frame: Up to 60 months]
• Disease Response to Treatment - Systemic Lupus Erythematosus [Time frame: Up to 60 months]
• Disease Response to Treatment - Lupus Nephritis [Time frame: Up to 60 months]
• Disease Response to Treatment - Idiopathic Inflammatory Myopathy [Time frame: Up to 60 months]
• Disease Response to Treatment - Systemic Sclerosis [Time frame: Up to 60 months]
• Disease Response to Treatment - Systemic Sclerosis [Time frame: Up to 60 months]
• ALLO-329 Peak Expansion (Cmax) [Time frame: Up to 60 months]
• ALLO-329 Persistence Over Time Including Area Under the Expansion Curve (AUC) [Time frame: Up to 60 months]

Eligibility criteria

Inclusion criteria

• Adults ≥ 18 to < 75 years of age.
• Adequate hematological function and liver, cardiac, and pulmonary function.
• A highly sensitive urine pregnancy test or serum pregnancy test (for females of childbearing potential) negative at screening. All participants of childbearing potential must be willing to use a highly effective method of contraception for at least 12 months for females (6 months for males) after LD chemotherapy or ALLO-329 administration, whichever is later.
• Signed and dated informed consent form.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
• Confirmed active disease (SLE, IIM, or SSc) as defined by the appropriate classification criteria for each respective disease, clinical evidence, and/or laboratory testing.
• Disease activity as above despite prior treatment with standard of care therapy including at least one immunosuppressive agent for at least 3 months.

Exclusion criteria

• Participants with active systemic bacterial, fungal, or viral infection requiring systemic treatment or a clinically significant active, opportunistic, chronic or recurrent infection.
• Any active malignancy within 5 years prior to enrollment, except for adequately treated localized basal cell or squamous cell skin cancer, carcinoma in situ or low risk prostate cancer (Gleason score ≤ 6) under observation. Prior treatment of cancer with curative intent which in the opinion of the treating oncologist has less than a 10% chance of recurrence in the next 10 years can be allowed after discussion with the sponsor.
• Prior treatment with CD19 or CD70 targeted therapy or any prior engineered cell therapy (e.g., CAR T therapy), except prior treatment with ALLO-329 in this study.
• Clinically significant or unstable or uncontrolled acute or chronic disease (e.g., hypothyroidism and diabetes).
• Symptomatic cardiac or vascular disease requiring medical intervention within 6 months prior to screening, hemodynamically symptomatic pericardial effusion, or symptomatic electrocardiogram abnormality requiring medical intervention.
• Child-Pugh Class B or C cirrhosis.
• Symptomatic airway disease requiring medical intervention, pleural effusion ≥ Grade 2, or history of pulmonary embolism requiring anticoagulant therapy within 6 months of ALLO-329 dosing.
• Participants known to be refractory to platelet or red blood cell transfusions or who will refuse indicated transfusion support to manage cell counts following treatment.
• Any form of primary, inherited immunodeficiency.
• Unwilling to participate in an extended safety monitoring period.
• For participants with SLE: History or active disease involving CNS within the last 6 months or SLE that is drug-induced. For those with lupus nephritis, history of dialysis within 12 months prior to signing the informed consent form or expected need for renal replacement therapy within the next 12 months after dosing, or National Institutes of Health (NIH) chronicity score of 3+ in any of the following domains: glomerular sclerosis, glomerular fibrous crescents, tubular atrophy, and/or interstitial fibrosis.
• Participants with IIM: A myositis other than specified classification per exclusion criteria, non-reversible, unrelated or weakness not amenable to assessment, or dermatomyositis with presence of anti-TIF1 gamma antibody.
• Participants with SSc: Pulmonary arterial hypertension requiring treatment, rapidly progressive or severe SSc gastrointestinal involvement, or prior scleroderma renal crisis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• Mayo Clinic — Phoenix
• Loma Linda University Medical Center — Loma Linda
• University of Colorado Denver — Aurora
• Mayo Clinic — Jacksonville
• The University of Chicago Medical Center — Chicago
• University of Iowa — Iowa City
• University of Kansas Medical Center — Kansas City
• Norton Cancer Institute, St. Matthews Campus — Louisville
• … and 6 more centers

Canada · 1 center

• Hôpital Maisonneuve Rosemont — Montreal

Identifiers

NCT: NCT07085104 · ALLO-329-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗