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

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 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).

Study Overview

• Status: Recruiting
• Conditions: Systemic Sclerosis; Idiopathic Inflammatory Myopathy; Systemic Lupus Erythematosus (With and Without Nephritis)
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Genetic: ALLO-329

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Allogene Therapeutics, Inc.; Phone Number: +1 415-604-5696; Email: clinicaltrials@allogene.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • Hôpital Maisonneuve Rosemont
      • Principal Investigator: Nicolas Richard, MD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Vivek Nagaraja, MD
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University Medical Center
      • Principal Investigator: Hisham Abdel-Azim, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver
      • Principal Investigator: Melissa Griffith, MD
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Vikas Majithia, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center
      • Principal Investigator: Michael Macklin, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Principal Investigator: Hanna Zembrzuska, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute, St. Matthews Campus
      • Principal Investigator: Don Stevens, MD
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care
      • Principal Investigator: Birju Bhatt, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Margrit Wiesendanger, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Lisa Criscione-Schreiber, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29605
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Melissa Cunningham, MD
    • Greenville, South Carolina, United States, 29425
      • Recruiting
      • Prisma Health
      • Principal Investigator: Cory McGee, MD
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Recruiting
      • LDS Hospital - lntermountain Health
      • Principal Investigator: Pankhuri Gupta, MD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALLO-329, Cyclophosphamide; Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide.	Drug: Cyclophosphamide; Chemotherapy for lymphodepletion; Genetic: ALLO-329; An allogeneic CAR T cell therapy targeting CD19 and CD70
Experimental: ALLO-329; Participants receive ALLO-329 without a lymphodepletion regimen.	Genetic: ALLO-329; An allogeneic CAR T cell therapy targeting CD19 and CD70
Experimental: ALLO-329, Cyclophosphamide, Fludarabine; Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide and fludarabine.	Drug: Fludarabine; Chemotherapy for lymphodepletion; Drug: Cyclophosphamide; Chemotherapy for lymphodepletion; Genetic: ALLO-329; An allogeneic CAR T cell therapy targeting CD19 and CD70

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting toxicities (DLTs) and Other Safety Parameters	The incidence of dose limiting toxicities (DLTs) and other safety parameters (including but not limited to treatment emergent adverse events [AEs], serious adverse events [SAEs], and clinical laboratory abnormalities)	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Response to Treatment - Systemic Lupus Erythematosus	Efficacy as assessed by rates of achieving SRI-4, LLDAS and DORIS remission.	Up to 60 months
Disease Response to Treatment - Systemic Lupus Erythematosus	Efficacy as assessed by change from baseline in SLEDAI-2K score.	Up to 60 months
Disease Response to Treatment - Lupus Nephritis	Efficacy as assessed by complete renal response (CRR) and partial renal response (PRR).	Up to 60 months
Disease Response to Treatment - Idiopathic Inflammatory Myopathy	Efficacy as assessed by ACR/EULAR myositis response criteria components.	Up to 60 months
Disease Response to Treatment - Systemic Sclerosis	Efficacy as assessed by change from baseline in the European Scleroderma Trials and Research Group (EUSTAR) activity index.	Up to 60 months
Disease Response to Treatment - Systemic Sclerosis	Efficacy as assessed by change from baseline in the American College of Rheumatology Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (ACR-CRISS).	Up to 60 months
ALLO-329 Peak Expansion (Cmax)		Up to 60 months
ALLO-329 Persistence Over Time Including Area Under the Expansion Curve (AUC)		Up to 60 months

Collaborators and Investigators

• Sponsor: Allogene Therapeutics
• Investigators: Study Director: Allogene Study Director, Allogene Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): October 1, 2032

Study Registration Dates

• First Submitted: July 8, 2025
• First Submitted That Met QC Criteria: July 23, 2025
• First Posted (Actual): July 25, 2025

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: SLE; Myositis; Dermatomyositis; CD19; Systemic lupus erythematosus; CAR T; Autoimmune disease; IIM; Scleroderma; Lupus nephritis; Systemic sclerosis; AlloCAR T; Idiopathic inflammatory myopathy; Anti-synthetase syndrome; LN; SSc; CD70; Allogeneic CAR T
• Additional Relevant MeSH Terms: Urogenital Diseases; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neuromuscular Diseases; Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Glomerulonephritis; Nephritis; Polymyositis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Autoimmune Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Dermatomyositis; Myositis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: ALLO-329-101

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