AzTrials
AzTrials

Autoimmune DisordersPhase 1/2NCT06434363

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

A Phase 1/2 study testing Tafasitamab, Fludarabine phosphate and Cyclophosphamide in people with Autoimmune Disorders and Systemic Sclerosis, run by M.D. Anderson Cancer Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tafasitamab, Fludarabine phosphate and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
2 sitesUnited States
Study dates
31 Jul 2024to 31 Dec 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • SSc Specific Inclusion Criteria
  • Diagnosis of SSc defined as follows:
  • 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.
  • SSc disease activity i) Diffuse SSc meeting the following criteria:
  • 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):
Show all 42Show fewer
  • 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):
  • Increased extent or severity of traction bronchiectasis and bronchiolectasis.
  • New ground-glass opacity with traction bronchiectasis (iii) New fine reticulation (iv) Increased extent or increased coarseness of reticular abnormality.
  • 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
  • SLE Specific Inclusion Criteria
  • 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:
  • 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.
  • If a subject is currently receiving:
  • 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.
  • Regarding oral corticosteroid, doses <0.5 mg/kg prednisone equivalent at the time of enrollment are required. Steroid taper to ≤10 mg prednisone equivalent prior to lymphodepleting chemotherapy is recommended.
  • Chronic GVHD specific inclusion criteria
  • The patient has a history of steroid resistant chronic graft versus host disease (SR- chronic GVHD) or is intolerant of or has unacceptable complications with steroids.
  • Definition of SR-chronic GVHD - Chronic GVHD that does not respond adequately to full-dose prednisone. Any of the following conditions would be considered SR-chronic GVHD:
  • Progressive symptoms / manifestations of chronic GVHD despite receiving prednisone 1 mg/kg/day (or equivalent) for two weeks
  • Stable symptoms / manifestations of chronic GVHD after four to six weeks of prednisone ≥0.5 mg/kg/day (or equivalent)
  • Inability to taper prednisone to <0.5 mg/kg/day (or equivalent) without worsening of symptoms / manifestations of chronic GVHD
  • Disease activity:
  • Manifestations/symptoms of chronic GVHD rated as moderate to severe on the NIH chronic GVHD global severity score.
  • Manifestations/symptoms of chronic GVHD that have not adequately responded or intolerant to both:
  • Ruxolitinib
  • Belumosudil.
  • May be receiving adrenal replacement doses of corticosteroids
  • Able to provide informed consent.
  • Age ≥18 to ≤80 years.
  • Adequate organ function i) Peripheral blood absolute neutrophil count (ANC) ≥ 1 × 109/L, unless the neutropenia is deemed to be caused by the underlying autoimmune disease.
  • Hemoglobin ≥ 8 g/dl, unless the anemia is deemed to be caused by the underlying autoimmune disease.
  • Platelet count ≥ 50 × 109/L without platelet transfusion support, unless the thrombocytopenia is deemed to be caused by the underlying autoimmune disease. No clinically significant active bleeding.
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) and total bilirubin ≤ 3 × ULN (or direct bilirubin ≤ 3 × ULN with documented Gilbert's syndrome).
  • Oxygen saturation (SaO2) ≥ 92% on room air (as measured by forehead probes in SSc patients).
  • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 45% as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  • Adequate renal function, defined as serum creatinine ≤ 2x ULN and estimated Glomerular Filtration Rate (eGFR using the CKD-EPI equation) ≥ 30 ml/min/1.73 m2 5. Recovery to ≤ Grade 1 or baseline of any non-hematological toxicities due to prior therapy.
  • 6. Negative pregnancy test in WOCBP. 7. All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of therapy. Acceptable forms of birth control for female patients include hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor. Participant is willing and able to adhere to the study visit schedule and other protocol requirements and willing to sign informed consent.

Who cannot join

  • SSc specific exclusion criteria
  • 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.
  • SLE specific Exclusion Criteria
Show all 30Show fewer
  • 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:
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or unwillingness or inability to follow the procedures required in the protocol.
  • Active, clinically significant central nervous system pathology
  • Prior history of malignancies or lymphoproliferative disease, following are allowed: Basal or squamous cell carcinoma of the skin, Carcinoma in situ of the cervix or breast or Smoldering Myeloma. History of malignancy that has been treated with a curative intent and is in remission may be allowed after discussion with PI.
  • Active hepatitis C, active syphilis, any human immunodeficiency virus (HIV), human lymphocytic T-cell virus type 1 and/or type 2 (HTLV-1 and/or HTLV-2
  • Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate anti- infective treatment at screening or within 72 hours before LD chemotherapy, or 5 days before AD-PluReceptor administration.
  • History of any one of the following cardiovascular conditions within the 6 months prior to screening: Class III or IV heart failure as defined by the New York Heart Association, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
  • Prior CAR T cell therapy, genetically modified T cell therapy.
  • Treatment with cyclophosphamide within 3 days, tocilizumab within 9 weeks, and/or any other immunosuppressive drug (excluding steroids) within 5 half-lives prior to administration of lymphodepleting chemotherapy. Immunosuppressive medications are allowed if not being used for management of SLE, LN or SSc.
  • Treatment with mycophenolate mofetil within 4 days prior to administration of lymphodepleting chemotherapy. For patients who will receive tafasitamab alone may continue mycophenolate mofetil throughout the study.
  • History of anaphylactic or severe systemic reaction to FLU, CY, Tafasitamab, or any of their metabolites.
  • Uncontrolled infection at screening.
  • Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal (on TPN), pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
  • Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Chitra Chitra Hosing, MD contact

(713) 745-3219

cmhosing@mdanderson.org

United States2 sites, 2 recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Chitra Chitra, MD, 713-745-3219, cmhosing@mdanderson.org

    Chitra Hosing, MD

    Recruiting

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

    Shervin Assassi, MD, 713-500-7118, shervin.assassi@uth.tmc.edu

    Shervin Assassi, MD

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

Primary Objectives:

To determine the safety, tolerability and optimal cell dose of AD-PluReceptor plus Tafasitamab cxix and lymphodepleting chemotherapy in patients with systemic sclerosis and systemic lupus erythematosus (including lupus nephritis).

Secondary Objectives:

To assess the overall response rate.

To evaluate the persistence and kinetics of infused allogeneic donor AD-PluReceptor cells in the recipient.

To conduct comprehensive immune reconstitution studies.

To evaluate the number of patients not requiring any systemic immunosuppressive therapy for their autoimmune disease at 1 year post infusion.

Being tested
Tafasitamab, Fludarabine phosphate, Cyclophosphamide, Tafasitamab and NK cells
Keywords
CAR NK, CAR, Natural Killer, SSc, SLE, LN, GVHD, Chronic GVHD
Medical subject headings
Autoimmune Diseases, Scleroderma, Systemic, Lupus Erythematosus, Systemic, Lupus Nephritis, Graft vs Host Disease, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06434363
Study groupRoleWhat they receive
Safety Lead-InExperimentalNot described
Receives: Drug: Tafasitamab
Dose EscalationExperimentalNot described
Receives: Drug: Tafasitamab; Drug: Fludarabine phosphate; Drug: Cyclophosphamide; Drug: Tafasitamab and NK cells
Dose ExpansionExperimentalNot described
Receives: Drug: Tafasitamab; Drug: Fludarabine phosphate; Drug: Cyclophosphamide; Drug: Tafasitamab and NK cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion; an average of 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2024
  2. Study start31 Jul 2024
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
47 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06434363
Sponsor's protocol ID
2024-0208
Other IDs
NCI-2024-04434
Status last verified
Oct 2026
First submitted
23 May 2024
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tafasitamab, Fludarabine phosphate and Cyclophosphamide in people with Autoimmune Disorders and Systemic Sclerosis, run by M.D. Anderson Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Chitra Chitra Hosing, MD ((713) 745-3219, cmhosing@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Event (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06434363.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in