Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders

NCT06434363 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0208NCI-2024-04434
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of Safety Lead-In is to confirm the safety of tafasitamab when given to patients with SSc, SLE, and LN. The goal of Phase 1 is to find the recommended dose of AD-PluReceptor-NK cells in combination with tafasitamab and lymphodepleting chemotherapy that can be given to patients with the disease. The goal of Phase 2 is to learn if the dose of AD-PluReceptor-NK cells found in Phase 1 in combination with tafasitamab and lymphodepleting chemotherapy can help to control the disease.

Conditions

Systemic Sclerosis; Systemic Lupus Erythematosus; Lupus; Lupus Nephritis; Autoimmune Disorders

Keywords

CAR NK, CAR, Natural Killer, SSc, SLE, LN, GVHD, Chronic GVHD

Outcome Measures

Primary Outcomes (1)

• Adverse Event

  ncidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (3)

Safety Lead-In

EXPERIMENTAL

Drug: Tafasitamab

Dose Escalation

EXPERIMENTAL

Drug: Tafasitamab; Drug: Fludarabine phosphate; Drug: Cyclophosphamide; Drug: Tafasitamab and NK cells

Dose Expansion

EXPERIMENTAL

Drug: Tafasitamab; Drug: Fludarabine phosphate; Drug: Cyclophosphamide; Drug: Tafasitamab and NK cells

Interventions

Cyclophosphamide DRUG

Given by vein (IV)

Dose Escalation; Dose Expansion

Tafasitamab and NK cells DRUG

Given by vein (IV)

Dose Escalation; Dose Expansion

Tafasitamab DRUG

Given by vein (IV)

Dose Escalation; Dose Expansion; Safety Lead-In

Fludarabine phosphate DRUG

Given by vein (IV)

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Diagnosis of SSc defined as follows:
• i) Fulfilling 2013 American College of Rheumatology (ACR)and European League Against Rheumatism classification (EULAR) criteria for SSc.46 ii) Antinuclear Antibody (ANA) by immunofluorescence positive at titer ≥ 1:80 at screening or prior to screening.
• B. SSc disease activity i) Diffuse SSc meeting the following criteria:
• (1) Disease duration ≤ 7 years (from onset of first non-Raynaud manifestation) AND (2) mRSS ≥ 15 at screening (Appendix 1) OR ii) Participants diagnosed with diffuse or limited cutaneous SSc AND presence of ILD changes on HRCT AND Disease duration ≤ 7 years (from onset of first non- Raynaud manifestation) AND either (1) or (2)
• Progressive ILD as defined by Raghu et al47 (≥ 2 of the following):
• (a) worsening respiratory symptoms (b) physiological evidence of disease progression (≥ 1 of the following): (i) Absolute decline in FVC ≥ 5% predicted within 1 year of follow-up (ii) Absolute decline in DLCO (corrected for Hb) ≥ 10% predicted within 1 year of follow-up radiological evidence of disease progression (c) radiological evidence of disease progression (≥ 1 of the following):
• (i) Increased extent or severity of traction bronchiectasis and bronchiolectasis.
• (ii) New ground-glass opacity with traction bronchiectasis (iii) New fine reticulation (iv) Increased extent or increased coarseness of reticular abnormality.
• (v) New or increased honeycombing (vi) Increased lobar volume loss
• FVC \< 80% predicted or extent of ILD changes on HRCT \> 20%. C. Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, and/or tocilizumab
• A clinical diagnosis of SLE, based on the 2019 EULAR/ ACR classification criteria for adult SLE.
• Positive ANA titer ≥1:80 or positive anti-dsDNA antibody at screening or prior to screening.
• For LN subjects only: Active, biopsy-proven lupus nephritis (kidney biopsy should have been done within 1 year of study enrollment) class III or IV, with or without the presence of Class V, using the 2018 Revised International Society of Nephrology/Renal Pathology Society criteria48.
• Diagnosed with active SLE. Subjects with either LN or without LN will be eligible if they meet the following criteria:
• a. For LN subjects: urine protein-to-creatinine ratio (UPCR) ≥0.5 g/g on 2 first morning void urine samples during screening despite prior or current treatment with standard of care therapy for at least 12 weeks, including corticosteroids, MMF/mycophenolic acid (MPA), CY, calcineurin inhibitors, belimumab, and/or rituximab. Patients should have failed at least 2 standard of care immunosuppressive therapies tried for 3 months, b. For non-renal SLE subjects: SLEDAI-2K ≥8 and clinical SLEDAI-2K ≥6 (excluding headache, alopecia, mucosal ulcers, fever, and organic brain syndrome) or ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system) during screening despite prior or current treatment with standard of care therapy, including corticosteroids, rituximab or other B cell depleting agents, CY, MMF/MPA, azathioprine, methotrexate, 6-mercaptopurine, sirolimus, tacrolimus, thalidomide, leflunomide, mizorbine, anifrolumab, and/or belimumab. Patients should have failed at least 2 standard of care immunosuppressive therapies tried for 3 months, or failed due to intolerance, or unable to obtain medication.

You may not qualify if:

• SSc related pulmonary arterial hypertension (PAH) requiring active treatment.
• Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia.
• Prior scleroderma renal crisis.
• Severe pulmonary dysfunction with a hemoglobin corrected DLC0 \< 40% or FVC \< 40% of predicted or O2 saturation \< 92% at rest without supplemental oxygen as measured by forehead oxygen pulse oximetry.
• Subjects are excluded from the study if any of the following criteria apply:
• For LN subjects only: Evidence of severe chronicity on kidney biopsy, defined as a modified National Institute of Health chronicity index score of 3+ for any of the following
• individual biopsy features: total glomerulosclerosis score, fibrous crescents, tubular atrophy, or interstitial fibrosis.
• The presence of biopsy-proven kidney disease other than active lupus nephritis
• Severe pulmonary dysfunction with a hemoglobin corrected DLC0 \< 40% or FVC \< 40% of predicted or O2 saturation \< 92% at rest without supplemental oxygen as measured by forehead oxygen pulse oximetry.Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening.
• Treatment with any immunosuppressive drug (except steroids) within 5 half lives prior to administration of lymphodepleting therapy.
• Immunosuppressive Drug Five Half Lives Half Life of the Drug Axatilimab 23 days 108 hours Belumosudil 4 days 19 hours Cyclophosphamide 3 days 3-12 hours Ibrutinib 2 days 4-6 hours Ruxolitinib 2 days 5.8 hours Sirolimus 13 days 62 hours Tacrolimus 8 days 2.1-36 hours Tocilizumab 9 weeks 5-13 days
• Receiving any immunosuppressive medications that are not being used for management of chronic GVHD.
• Treatment with steroids ≥0.5 mg/kg prednisone daily or equivalent at the time of enrollment and \>10 mg prednisone daily or equivalent at the time of lymphodepletion.
• Received rituximab within 6 months of lymphodepletion.
• Subjects are excluded from the study if any of the following medical conditions apply:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Autoimmune Diseases; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Lupus Nephritis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

tafasitamab; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Chitra Hosing, MD

  MDAnderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chitra Chitra Hosing, MD

CONTACT

(713) 745-3219; cmhosing@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 30, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (2)