Recruiting
Phase 1

WS-CART-CS1

Sponsor:

Washington University School of Medicine

Code:

NCT06185751

Conditions

Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

WS-CART-CS1

Lymphodepleting chemotherapy

Study Details

Brief summary:

Despite recent therapeutic advances, multiple myeloma (MM) remains an incurable disease. Although survival has improved, there are nevertheless diminishing durations of response to each subsequent line of therapy. This highlights the need for further therapeutic innovation. BCMA-targeting CAR-T cells show impressive response rates; however, their median duration of response is disappointing. The investigators propose that CS1(SLAMF7)-targeting CAR-T cells will fill a gap in the MM armamentarium.

CS1 is an attractive target in MM because it is expressed in most patients. Elotuzumab (Empliciti®), an approved anti-CS1 antibody, has proven the clinical efficacy of this target. CAR-T cells are an ideal modality to target CS1, given that two approved treatments, ide-cel (idecabtagene vicleucel, AbecmaTM) and cilta-cel (ciltacabtagene autoleucel, Carvykti™), have proven the potential for cellular immunotherapy in MM.

The investigators are testing the safety and preliminary anti-myeloma efficacy of WS-CART-CS1, a CAR-T cell therapy targeting CS1.

Conditions

Multiple Myeloma

Study ID

NCT06185751

Start date

Aug 22, 2024

Status verified date

Jul, 2026

Completion date

Aug 31, 2040

Anticipated

Primary completion date

Aug 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Relapsed or refractory multiple myeloma after 3 or more prior lines of therapy, including proteasome inhibitor (e.g. bortezomib or carfilzomib), anti-CD38 therapy (e.g. daratumumab), and anti-BCMA therapies (e.g. BCMA bispecific antibodies or BCMA CAR-T)
  • Measurable disease, defined as meeting at least one of the following criteria:

  • Serum M-protein ≥ 0.5 g/dL
  • Urine M-protein ≥ 200 mg/24 h
  • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase) must be >10 mg/dL for consideration of defining progression before enrollment
  • A biopsy-proven plasmacytoma
  • Bone marrow plasma cells > 30% of total bone marrow cells
  • At least 18 years of age.
  • ECOG performance status ≤ 1
  • Adequate renal, hepatic, respiratory, and cardiovascular function, as defined below:

  • Renal function:

  • calculated creatinine clearance ≥ 50 mL/min/1.73 m2 OR
  • radioisotope glomerular filtration rate ≥ 50 mL/min/1.73 m2 OR
  • normal serum creatinine based on age/gender per institutional normal range
  • Hepatic function:

  • ALT (SGPT) ≤ 5 x ULN for age
  • Total bilirubin ≤ 2.0 x IULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin)
  • Respiratory function:

  • Minimum level of pulmonary reserve defined as oxygen saturation > 91% measured by pulse oximetry on room air
  • Cardiovascular function:

  • LVEF ≥ 45% confirmed by echocardiogram or MUGA within 28 days of screening
  • The effects of CS1 CAR-T on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (at least 2 forms of contraception, including one barrier method) prior to study entry and for 12 months after CS1 CAR-T infusion. If a female subject or female partner of a male subject becomes pregnant during therapy or within 12 months following WS-CART-CS1 infusion, the investigator must be notified in order to facilitate outcome follow-up.
  • Ability to understand and willingness to sign an IRB-approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Any prior systemic therapy for multiple myeloma within 14 days before planned day of leukapheresis.
  • A history of other malignancy with the exception of treated non-melanomatous skin cancers and malignancies for which all treatment was completed at least 2 years before registration and the subject has no evidence of disease.
  • Currently receiving any other investigational agents.
  • Receipt of any cellular therapy within 8 weeks prior to the planned start of conditioning.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CS1 CAR-T or other agents used in the study.
  • History of Grade 3 CRS or ICANS with other CAR-Ts (including BCMA CAR).
  • Active hepatitis B, active hepatitis C, any uncontrolled infection, or HIV infection.
  • Ongoing or active infection or other serious underlying medical condition that would impair the ability to receive protocol treatment.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Study Design

Enrollment

25 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A Dose Escalation: WS-CART-CS1

  • Undergo apheresis procedure for WS-CART-CS1 manufacturing.
  • Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician.
  • Lymphodepleting chemotherapy on days -5, -4, and -3.
  • Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused.
  • Part A is the dose escalation portion of the study.

experimental: Part B Dose Expansion: WS-CART-CS1

  • Undergo apheresis procedure for WS-CART-CS1 manufacturing.
  • Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician.
  • Lymphodepleting chemotherapy on days -5, -4, and -3.
  • Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused.
  • Part B is the dose expansion portion of the study. The dose of WS-CART-CS1 will be determined in Part A of the study.

Interventions

WS-CART-CS1

-Subject will be hospitalized for 7 days

Lymphodepleting chemotherapy

  • Cyclophosphamide 500 mg/m\^2 IV on Days -5, -4, and -3
  • Fludarabine 30 mg/m\^2 IV on Days -5, -4, and -3

Primary outcome measure

  • Part A: Frequency and severity of treatment-emergent adverse events [ Time Frame: From leukapheresis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week) ]
  • Part A: Frequency of dose-limiting toxicities (DLTs) [ Time Frame: From WS-CART-CS1 infusion through 28 days ]
  • Part B: Frequency and severity of treatment-emergent adverse events [ Time Frame: From leukaphereis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week) ]

Central Contacts and Locations

Central contacts

Armin Ghobadi, M.D.

314-747-2743arminghobadi@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Armin Ghobadi, M.D.

314-747-2743arminghobadi@wustl.edu

Principal Investigator:

Armin Ghobadi, M.D.

More Information

Sponsor

Washington University School of Medicine

Last update posted

Jul 9, 2026

Last verified

Jul, 2026

Keywords

  • Chimeric Antigen Receptor
  • CS1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-07-09.