RECRUITING

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

Conditions

Multiple Myeloma Chimeric Antigen Receptor CS1

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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

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.

Official Title

Phase 1 Dose-Escalation and Dose-Expansion Study of the Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in Subjects With Multiple Myeloma

Quick Facts

Study Start:2024-08-22

Study Completion:2040-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06185751

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
* 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).	* 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.

Inclusion Criteria

Exclusion 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).

* 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.

Contacts and Locations

Study Contact

Armin Ghobadi, M.D.

CONTACT

314-747-2743

arminghobadi@wustl.edu

Principal Investigator

Armin Ghobadi, M.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Armin Ghobadi, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

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 Date2024-08-22

Study Completion Date2040-08-31

Study Record Updates

Study Start Date2024-08-22

Study Completion Date2040-08-31

Terms related to this study

Keywords Provided by Researchers

Chimeric Antigen Receptor
CS1

Additional Relevant MeSH Terms

Multiple Myeloma