Off-the-shelf CAR T-cell treatment (ALLO-329) for adults with lupus, inflammatory myopathy, or systemic sclerosis

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

This trial tests ALLO-329, an off-the-shelf CAR T-cell therapy, to see if it is safe and helps adults with active SLE (with or without kidney involvement), idiopathic inflammatory myopathy, or systemic sclerosis.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 69 Years
• Sex: All
• Sponsor: Allogene Therapeutics (industry)
• Drugs / interventions: CAR T, chemotherapy, chimeric antigen receptor
• Locations: 13 sites (Phoenix, Arizona and 12 other locations)
• Trial ID: NCT07085104 on ClinicalTrials.gov

What this trial studies

This first-in-human, single-arm, open-label Phase 1 trial gives participants lymphodepleting chemotherapy followed by a single infusion of ALLO-329, an allogeneic dual CAR T-cell product targeting CD19 and CD70, to observe safety and early signs of activity. The study enrolls adults with active SLE (with or without nephritis), idiopathic inflammatory myopathy, or systemic sclerosis whose disease persists despite standard immunosuppressive therapy. Primary aims are to characterize safety and tolerability, identify a recommended Phase 2 regimen, and collect preliminary biological and clinical response data. Participants are followed with clinical assessments and laboratory testing to track adverse events, immune effects, and changes in disease activity.

Who should consider this trial

Good fit: Adults aged 18 to under 70 with confirmed active SLE, idiopathic inflammatory myopathy, or systemic sclerosis that has persisted despite at least one immunosuppressive agent (plus standard care) and who have adequate organ function and agree to required contraception are ideal candidates.

Not a fit: People with mild disease controlled by standard therapy, significant organ dysfunction, active infections, pregnancy, or other contraindications to lymphodepletion or CAR T-cell therapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, ALLO-329 could induce meaningful reductions in disease activity or durable remissions for people with autoimmune conditions that have not responded to standard treatments.

How similar studies have performed: Autologous anti-CD19 CAR T-cell therapies have shown promising results in small case series for refractory SLE, but ALLO-329 as an allogeneic dual-target CAR T approach is first-in-human and therefore largely untested.

Eligibility criteria

Inclusion Criteria:

1. Adults ≥ 18 to \< 70 years of age.
2. Adequate hematological function and liver, cardiac, and pulmonary function.
3. 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 (6 months for males) after LD chemotherapy or ALLO-329 administration, whichever is later.
4. Signed and dated informed consent form.
5. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
6. Confirmed active disease (SLE, IIM, or SSc) as defined by the appropriate classification criteria for each respective disease, clinical evidence, and/or laboratory testing.
7. Disease activity as above despite prior treatment with standard of care therapy including at least one immunosuppressive agent for at least 3 months (in addition to hydroxychloroquine \[HCQ\]).

Exclusion Criteria:

1. Participants with active systemic bacterial, fungal, or viral infection requiring systemic treatment or a clinically significant active, opportunistic, chronic or recurrent infection.
2. 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).
3. Prior treatment with CD19 or CD70 targeted therapy or any prior engineered cell therapy (e.g., CAR T therapy).
4. Clinically significant or unstable or uncontrolled acute or chronic disease (e.g., hypothyroidism and diabetes) not due to SLE/IIM/SSc.
5. 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.
6. Child-Pugh Class B or C cirrhosis.
7. Symptomatic airway disease requiring medical intervention, pleural effusion ≥ Grade 2, or history of pulmonary embolism requiring anticoagulant therapy within 6 months of enrollment.
8. 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.
9. Any form of primary, inherited immunodeficiency.
10. Unwilling to participate in an extended safety monitoring period.
11. For participants with SLE: 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 or expected need for renal replacement therapy within the next 12 months, 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.
12. Participants with IIM: A myositis other than IIM classification, non-reversible, unrelated or weakness not amenable to assessment, or dermatomyositis with presence of anti-TIF1 gamma antibody.
13. Participants with SSc: Pulmonary arterial hypertension requiring treatment, rapidly progressive or severe SSc gastrointestinal involvement, or prior scleroderma renal crisis.

Where this trial is running

Phoenix, Arizona and 12 other locations

• Mayo Clinic — Phoenix, Arizona, United States (RECRUITING)
• University of Colorado Denver — Aurora, Colorado, United States (RECRUITING)
• Mayo Clinic — Jacksonville, Florida, United States (RECRUITING)
• The University of Chicago Medical Center — Chicago, Illinois, United States (RECRUITING)
• University of Iowa — Iowa City, Iowa, United States (RECRUITING)
• Norton Cancer Institute, St. Matthews Campus — Louisville, Kentucky, United States (RECRUITING)
• Astera Cancer Care — East Brunswick, New Jersey, United States (RECRUITING)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (RECRUITING)
• Duke University Medical Center — Durham, North Carolina, United States (RECRUITING)
• Medical University of South Carolina — Charleston, South Carolina, United States (RECRUITING)
• Prisma Health — Greenville, South Carolina, United States (RECRUITING)
• LDS Hospital - lntermountain Health — Salt Lake City, Utah, United States (RECRUITING)
• Hôpital Maisonneuve Rosemont — Montreal, Quebec, Canada (RECRUITING)

Study contacts

• Study coordinator: Allogene Therapeutics, Inc.

Conditions: Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathy, Systemic Sclerosis, Systemic lupus erythematosus, SLE, Lupus nephritis, LN, Idiopathic inflammatory myopathy