A Study to Investigate the Safety and Preliminary Efficacy of ALLO-329, an Allogeneic CAR T-cell Therapy, in Adults With Autoimmune Disease
Purpose
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).
Conditions
- Systemic Lupus Erythematosus (With and Without Nephritis)
- Idiopathic Inflammatory Myopathy
- Systemic Sclerosis
Eligibility
- Eligible Ages
- Between 18 Years and 69 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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 3 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 Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental ALLO-329, Cyclophosphamide |
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide. |
|
|
Experimental ALLO-329 |
Participants receive ALLO-329 without a lymphodepletion regimen. |
|
Recruiting Locations
Mayo Clinic
Phoenix 5308655, Arizona 5551752 85054
Phoenix 5308655, Arizona 5551752 85054
University of Iowa
Iowa City 4862034, Iowa 4862182 52242
Iowa City 4862034, Iowa 4862182 52242
Norton Cancer Institute, St. Matthews Campus
Louisville 4299276, Kentucky 6254925 40207
Louisville 4299276, Kentucky 6254925 40207
Astera Cancer Care
East Brunswick 5097402, New Jersey 5101760 08816
East Brunswick 5097402, New Jersey 5101760 08816
Icahn School of Medicine at Mount Sinai
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10029
Duke University Medical Center
Durham 4464368, North Carolina 4482348 27710
Durham 4464368, North Carolina 4482348 27710
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29605
Charleston 4574324, South Carolina 4597040 29605
Prisma Health
Greenville 4580543, South Carolina 4597040 29425
Greenville 4580543, South Carolina 4597040 29425
LDS Hospital - lntermountain Health
Salt Lake City 5780993, Utah 5549030 84143
Salt Lake City 5780993, Utah 5549030 84143
More Details
- NCT ID
- NCT07085104
- Status
- Recruiting
- Sponsor
- Allogene Therapeutics