Multiple myeloma (MM) MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: SLAMF7 CAR-T
Product Code: [NA]
Pharmaceutical Form: Suspension for injection
Current Sponsor code: SLAMF7 CAR-T
Concentration unit: thousand organisms/ml thousand organisms/millilitre
C
Sponsors
Universitätsklinikum Würzburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form 2. Patient is >=18 years of age 3. Patient is willing and able to adhere to the protocol requirements 4. Patient with diagnosis of MM who has been treated with at least 2 prior lines of treatment, including at least one cycle of high-dose chemotherapy with autologous hematopoietic stem cell transplantation if the patient was eligible, and exposure to an immunomodulatory imide drug (e.g. lenalidomide and/or pomalidomide), a proteasome inhibitor, and/or an anti-CD38 antibody. 5. At least one of the following subcriteria must be measured in the patient: - Serum M-protein greater or equal to 0.5 g/dL - Urine M-protein greater or equal to 200 mg/24 h - Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal - A biopsy-proven evaluable plasmacytoma - Bone marrow plasma cells >10% of total bone marrow cells (>30% if bone marrow plasma cells are the only marker of measurable disease) 6. Patients previously treated with an anti-SLAMF7 antibody are eligible. 7. Karnofsky performance status >=60%. If patient has a Karnofsky performance status =65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning 12 months, and suffers on chronic Graft-versus-Host Disease and/or is on systemic immune-suppressants. 3. Patient with diagnosis of MM a. in first relapse following an autologous stem cell transplantation or b. in second relapse that subsequently achieves a complete response that is considered being a candidate for an allogeneic stem cell transplantation, unless the patient explicitly denies undergoing an allogeneic stem cell transplantation. 4. Patient has received anti-CD38 and/or anti-SLAMF7 antibodies 2.5 x upper limit of normal (ULN) and total bilirubin >1.5 x ULN (unless due to Gilbert’s syndrome and direct bilirubin is 1.5 x ULN, unless on a stable dose of anti-coagulant. 10. Evidence of human immunodeficiency virus (HIV) infection. 11. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV), excluding - Patients who are hepatitis B surface antigen negative and HBV viral deoxyribonucleic acid (DNA) negative - Patients who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months - Patients who are seropositive because of hepatitis B virus vaccine - Patients with known HBV infection but undetectable HBV viral load and on anti-viral therapy to prevent HBV reactivation. 12. Seropositive for and with active viral infection with hepatitis C virus (HCV), excluding - Patients who had hepatitis C but had received an antiviral treatment and show no detectable HCV viral ribonucleic acid (RNA) for 6 months. 13. Seropositive for syphilis on treponema pallidum hemagglutination test, excluding - Patients with negative treponema pallidum antibody absorption test result 14. Patients with active infection (e.g. asymptomatic and symptomatic severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) or other serious medical or psychiatric disorder on investigators decision. 15. Pregnant or lactating women. 16. Current or previous (within 30 days of enrollment) treatment with another IMP. 17. Known abuse of alcohol, drugs, or medicinal products. 18. Employees of the sponsor, or employees or relatives of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1) Phase I: Type, frequency, and severity of adverse events (AEs), including serious adverse events (SAEs), cytokine release syndrome (CRS), and neurotoxicity (i.e. immune effector cell-associated neurotoxicity syndrome [ICANS]) 2) Phase I: MTD of SLAMF7 CAR-T that can be administered in phase IIa will be assessed at the end of phase I 3) Phase IIa: Type, frequency, and severity AEs, including SAEs, CRS, and neurotoxicity (i.e. ICANS) 4) Phase IIa: Percentage of patients who achieved partial response (PR) or better using the IMWG Uniform Response Criteria for MM at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 after SLAMF7 CAR-T infusion;Timepoint(s) of evaluation of this end point: 1) D0, 4 hours after infusion, D1 to D28, W5, W6, W7, W8, W10, W12, M4 to M12, M15, M18, M24 2) End of phase I 3) D0, 4 hours after infusion, D1 to D28, W5, W6, W7, W8, W10, W12, M4 to M12, M15, M18, M24 4) M1 to M6, M9, M12, M15, M18, M21, M24;Main Objective: 1) Phase I: Safety determination of the treatment with SLAMF7 CAR-T 2) Phase I: Determination of the MTD and the recommended phase IIa dose of SLAMF7 CAR-T 3) Phase IIa: Safety determination of the treatment with SLAMF7 CART 4) Phase IIa: Evaluation of the efficacy, defined as overall response rate (ORR) of SLAMF7 CAR-T in patients with MM;Secondary Objective: 1) Evaluation of the complete response (CR) of SLAMF7 CAR-T in patients with MM 2) Determination of the feasibility to ex vivo manufacture of autologous SLAMF7 CAR-T and to administer to patients with MM 3) Determination of the expansion and duration of in vivo persistence of adoptively transferred SLAMF7 CAR- T cells in peripheral blood, bone marrow and tumor tissue 4) To determine if the adoptive transfer of SLAMF7 CAR-T has an antimyeloma effect 5) Determination of the SLAMF7 CAR-T cells impact on patient's overall survival (OS) 6) To determine if the adoptive transfer of SLAMF7 CAR-T affects the quality of life | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Phase IIa: Percentage of patients who achieved CR or better using the IMWG Uniform Response Criteria for MM at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 after SLAMF7 CAR-T infusion 2) Phase I and IIa: Percentage of MM patients enrolled into the trial who receive ex vivo expanded autologous SLAMF7 CAR-T within the 48h shelf-life of the product 3) Phase I and IIa: Maximum peak in SLAMF7 CAR-T (Cmax), time to peak of SLAMF7 CAR-T (Tmax), area under the curve of CAR-T CD4+ and CD8+ cells (AUC), including maximum expansion and duration of persistence of SLAMF7 CAR-T cells at Baseline, Days 1, 3, 7, 10, 14, 21, 28, Week 6, 8, 12, Months 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24 4.) Phase I and IIa: a) Time between first SLAMF7 CAR-T infusion and first documentation of response at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24; b) Time between first response and disease progression PD or death at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24 c) Time between SLAMF7 CAR-T infusion and first documentation of PD or death at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24 d) Proportion of minimal residual disease (MRD) evaluable patients that are MRD negative (defined at a minimum of 1 in 105 nucleated cells) using flow cytometry at Months 1, 3, 6, 12, 24 5) Phase I and IIa: Time between SLAMF7 CAR-T infusion and time of death at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24 6) Phase I and IIa: Patient-reported outcomes as measured by EORTC-QLQ-C30/-MY20 at Screening, Baseline, Months 6, 12, 24;Timepoint(s) of evaluation of this end point: 1) M1 to M6, M9, M12, M15, M18, M21, M24 2) D0 3) Baseline (BL) (D-8), D1, D3, D7, D10, D14, D21, D28, W6, W8, W12, M4 to M12, M15, M18, M21, M24 4.a) M1 to M6, M9, M12, M15, M18, M21, M24 4.b) M1 to M6, M9, M12, M15, M18, M21, M24 4.c) M1 to M6, M9, M12, M15, M18, M21, M24 4.d) M1, M3, M6, M12, M24 5) M1 to M6, M9, M12, M15, M18, M21, M24 6) M6, M12, M24 | — |
Countries
France, Germany, Italy, Spain
Contacts
Public ContactUfficio Ricerche Ciniche - Stem Cel
IRCCS Ospedale San Raffaele
Outcome results
None listed