RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-07-31

Study Completion:2030-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06434363

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Progressive ILD as defined by Raghu et al47 (≥ 2 of the following): 1. worsening respiratory symptoms 2. physiological evidence of disease progression (≥ 1 of the following): 2. FVC \< 80% predicted and moderate to severe ILD, as assessed by a radiologist. C. Inadequate response to at least 2 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, and/or tocilizumab. 1. A clinical diagnosis of SLE, based on the 2019 EULAR/ ACR classification criteria for adult SLE. 2. Positive ANA titer ≥1:80 or positive anti-dsDNA antibody at screening. 3. For LN subjects only: Active, biopsy-proven lupus nephritis (kidney biopsy should have been done within 6 months 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. 4. Diagnosed with active SLE. Subjects with either LN or without LN will be eligible if they meet the following criteria: 1. For LN subjects: urine protein-to-creatinine ratio (UPCR) ≥1 mg/mg 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, 2. For non-renal SLE subjects: SLEDAI-2K ≥8 and clinical SLEDAI-2K ≥6 (excluding headache, alopecia, mucosal ulcers, fever, and organic brain syndrome) 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 tired for 3 months. 5. If a subject is currently receiving: 1. Standard immunosuppressive therapy (including MMF/MPA, CY, azathioprine, antimalarial therapy, methotrexate, 6-mercaptopurine, sirolimus, tacrolimus, thalidomide, leflunomide, or mizorbine), the therapy must have been initiated at least 12 weeks prior to screening and on a stable dose for at least 8 weeks prior to screening, except for dose reduction due to safety or tolerability. 2. A renin-angiotensin-aldosterone inhibitor, (including direct renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and mineralocorticoid receptor blockers), the subject must be on a stable dose for at least 8 weeks prior to screening.A sodium-glucose cotransporter-2 (SGLT2) inhibitor, the subject must be on a stable dose for at least 8 weeks prior to screening. 3. Regarding oral corticosteroid, doses \<0.5 mg/kg prednisone equivalent at the time of infusion are required. 6. Adequate renal function, defined as: 1. For LN subjects: Estimated glomerular filtration rate of ≥45 mL/min/1.73m2 using the chronic kidney disease-epidemiology equation. 2. For non-renal SLE subjects: Estimated glomerular filtration rate of ≥60 mL/min/1.73m2 using the chronic kidney disease-epidemiology equation 1. SSc related pulmonary arterial hypertension (PAH) requiring active treatment. 2. Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia. 3. Prior scleroderma renal crisis. 4. Uncontrolled or rapidly progressive ILD (FVC \< 50; DLCO \< 50%); oxygen saturation (SaO2) \< 92% (room air at rest); or who have required mechanical breathing assistance (ventilator) within 1 year of signing informed consent. 1. Treatment with rituximab or other B cell-depleting agent within 26 weeks prior to screening, or within 12 weeks if there are laboratory results indicating presence of CD19+ B cells. 2. Treatment with voclosporin or other calcineurin inhibitor within 8 weeks prior to screening. 3. Treatment with anifrolumab, belimumab, or other biologic agent within 12 weeks prior to screening. 4. 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. 5. A diagnosis of antiphospholipid antibody syndrome by the 2006 Revised Sapporo International Consensus Criteria at the time of screening49 6. The presence of biopsy-proven kidney disease other than active lupus nephritis 7. Moderate-to-severe chronic pulmonary disease, including asthma requiring or refractory to medium or high-dose inhaled corticosteroids combined with other longer-acting medications, In subjects who have had pulmonary function tests: Spirometry results of forced expiratory volume (FEV1)/forced vital capacity \<0.7 and FEV1 \<80% predicted after bronchodilators, or diffusing capacity of the lungs for carbon monoxide results \<60% predicted. 8. Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Progressive ILD as defined by Raghu et al47 (≥ 2 of the following):
1. worsening respiratory symptoms
2. physiological evidence of disease progression (≥ 1 of the following):
2. FVC \< 80% predicted and moderate to severe ILD, as assessed by a radiologist. C. Inadequate response to at least 2 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, and/or tocilizumab.
1. A clinical diagnosis of SLE, based on the 2019 EULAR/ ACR classification criteria for adult SLE.
2. Positive ANA titer ≥1:80 or positive anti-dsDNA antibody at screening.
3. For LN subjects only: Active, biopsy-proven lupus nephritis (kidney biopsy should have been done within 6 months 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.
4. Diagnosed with active SLE. Subjects with either LN or without LN will be eligible if they meet the following criteria:
1. For LN subjects: urine protein-to-creatinine ratio (UPCR) ≥1 mg/mg 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,
2. For non-renal SLE subjects: SLEDAI-2K ≥8 and clinical SLEDAI-2K ≥6 (excluding headache, alopecia, mucosal ulcers, fever, and organic brain syndrome) 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 tired for 3 months.
5. If a subject is currently receiving:
1. Standard immunosuppressive therapy (including MMF/MPA, CY, azathioprine, antimalarial therapy, methotrexate, 6-mercaptopurine, sirolimus, tacrolimus, thalidomide, leflunomide, or mizorbine), the therapy must have been initiated at least 12 weeks prior to screening and on a stable dose for at least 8 weeks prior to screening, except for dose reduction due to safety or tolerability.
2. A renin-angiotensin-aldosterone inhibitor, (including direct renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and mineralocorticoid receptor blockers), the subject must be on a stable dose for at least 8 weeks prior to screening.A sodium-glucose cotransporter-2 (SGLT2) inhibitor, the subject must be on a stable dose for at least 8 weeks prior to screening.
3. Regarding oral corticosteroid, doses \<0.5 mg/kg prednisone equivalent at the time of infusion are required.
6. Adequate renal function, defined as:
1. For LN subjects: Estimated glomerular filtration rate of ≥45 mL/min/1.73m2 using the chronic kidney disease-epidemiology equation.
2. For non-renal SLE subjects: Estimated glomerular filtration rate of ≥60 mL/min/1.73m2 using the chronic kidney disease-epidemiology equation
1. SSc related pulmonary arterial hypertension (PAH) requiring active treatment.
2. Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia.
3. Prior scleroderma renal crisis.
4. Uncontrolled or rapidly progressive ILD (FVC \< 50; DLCO \< 50%); oxygen saturation (SaO2) \< 92% (room air at rest); or who have required mechanical breathing assistance (ventilator) within 1 year of signing informed consent.
1. Treatment with rituximab or other B cell-depleting agent within 26 weeks prior to screening, or within 12 weeks if there are laboratory results indicating presence of CD19+ B cells.
2. Treatment with voclosporin or other calcineurin inhibitor within 8 weeks prior to screening.
3. Treatment with anifrolumab, belimumab, or other biologic agent within 12 weeks prior to screening.
4. 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.
5. A diagnosis of antiphospholipid antibody syndrome by the 2006 Revised Sapporo International Consensus Criteria at the time of screening49
6. The presence of biopsy-proven kidney disease other than active lupus nephritis
7. Moderate-to-severe chronic pulmonary disease, including asthma requiring or refractory to medium or high-dose inhaled corticosteroids combined with other longer-acting medications, In subjects who have had pulmonary function tests: Spirometry results of forced expiratory volume (FEV1)/forced vital capacity \<0.7 and FEV1 \<80% predicted after bronchodilators, or diffusing capacity of the lungs for carbon monoxide results \<60% predicted.
8. Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Chitra Chitra Hosing, MD

CONTACT

(713) 745-3219

cmhosing@mdanderson.org

Principal Investigator

Chitra Hosing, MD

PRINCIPAL_INVESTIGATOR

MDAnderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Chitra Hosing, MD, PRINCIPAL_INVESTIGATOR, MDAnderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-07-31

Study Completion Date2030-12-31

Study Record Updates

Study Start Date2024-07-31

Study Completion Date2030-12-31

Terms related to this study

Additional Relevant MeSH Terms

Autoimmune Disorders
Systemic Sclerosis