Testing a new CAR-T therapy for multiple myeloma
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
This study tests a new CAR-T therapy to see if it can help people with tough-to-treat multiple myeloma feel better after other treatments haven't worked.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 25 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Washington University School of Medicine Academic / other |
| Drugs / interventions | daratumumab, CAR-T, CART, Elotuzumab, immunotherapy |
| Locations | 1 site (St Louis, Missouri) |
| Trial ID | NCT06185751 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and efficacy of CS1-targeting CAR-T cells in patients with relapsed or refractory multiple myeloma who have undergone multiple prior therapies. The study aims to determine how well these CAR-T cells can target and eliminate myeloma cells, potentially improving patient outcomes. Participants will receive lymphodepleting chemotherapy followed by the experimental CAR-T treatment. The trial focuses on patients with measurable disease and specific eligibility criteria to ensure a suitable candidate population.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory multiple myeloma after at least three prior lines of therapy.
Not a fit: Patients who have not undergone multiple lines of therapy or those with non-measurable disease may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with multiple myeloma who have limited treatment alternatives.
How similar studies have performed: Other studies using CAR-T therapies targeting different antigens in multiple myeloma have shown promising results, suggesting potential for success with this novel approach.
Eligibility criteria
Show full 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
* 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.
Where this trial is running
St Louis, Missouri
- Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Armin Ghobadi, M.D. — Washington University School of Medicine
- Study coordinator: Armin Ghobadi, M.D.
- Email: arminghobadi@wustl.edu
- Phone: 314-747-2743
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.