Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in Subjects With Multiple Myeloma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.
  • - Serum FLC assay: involved FLC level ≥10 mg/dL (100 mg/L) with abnormal serum FLC ratio.
  • - 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06185751
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Washington University School of Medicine
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Armin Ghobadi, M.D.
Principal Investigator Affiliation Washington University School of Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Study Website: View Trial Website
Arms & Interventions

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 with the starting dose of 0.5 x 10^6 cells/kg of WS-CART-CS1.

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

Biological: - WS-CART-CS1

-Subject will be hospitalized for 7 days

Drug: - 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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Washington University School of Medicine, Saint Louis, Missouri

Status

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Armin Ghobadi, M.D.

arminghobadi@wustl.edu

314-747-2743