AUTOLOGOUS T-CELLS TRANSDUCED WITH LENTIVIRAL VECTOR ENCODING AN ANTI-SLAMF7 CD28/CD3-ZETA CHIMERIC ANTIGEN RECEPTOR for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Signed informed consent form."}
• {"criterion_text":"- 2. Patient is ≥18 years of age."}
• {"criterion_text":"- 3. Patient is willing and able to adhere to the protocol requirements.3. Patient is willing and able to adhere to the protocol requirements."}
• {"criterion_text":"- 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 an anti-CD38 antibody. (Note: Induction therapy, up to 2 cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation, and subsequent consolidation and/or maintenance therapy are considered one line of treatment)."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 6. Patients previously treated with an anti-SLAMF7 antibody are eligible."}
• {"criterion_text":"- 7. Karnofsky performance status ≥60%. If patient has a Karnofsky performance status <60% (e.g. after a spinal cord injury) but is judged to be medically fit by the investigator, patient is eligible."}
• {"criterion_text":"- 8. Female patients of childbearing potential must: a) have a negative pregnancy test (blood) at screening. b) either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the IMP infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogenonly hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled. c) Agree to abstain from breast feeding during the study participation and for 1 year after the IMP infusion."}
• {"criterion_text":"- 9. Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after IMP infusion, even if he has undergone a successful vasectomy."}

Exclusion criteria

• {"criterion_text":"- 1. Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤12 months prior to leukapheresis."}
• {"criterion_text":"- 10. Evidence of human immunodeficiency virus (HIV) infection."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 13. Seropositive for syphilis on treponema pallidum hemagglutination test, excluding - Patients with negative treponema pallidum antibody absorption test result"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 15. Pregnant or lactating women."}
• {"criterion_text":"- 16. Current or previous (within 30 days of enrollment) treatment with another IMP."}
• {"criterion_text":"- 17. Known abuse of alcohol, drugs, or medicinal products."}
• {"criterion_text":"- 18. Employees of the sponsor, or employees or relatives of the investigator."}
• {"criterion_text":"- 2. 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 4. Patient has received anti-CD38 and/or anti-SLAMF7 antibodies ≤8 weeks prior to leukapheresis."}
• {"criterion_text":"- 5. Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or systemic steroids at any dose). (Note: Physiologic steroid replacement therapy, topical immunesuppresants as e.g. cyclosporine/tacrolimus eye drops, and topical steroids are permitted.)"}
• {"criterion_text":"- 6. Echocardiogram with left ventricular ejection fraction <45%."}
• {"criterion_text":"- 7. Inadequate renal function defined by creatinine clearance ≤45 mL/min using Cockcroft-Gault equation."}
• {"criterion_text":"- 8. Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >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 due to intrahepatic myeloma lesions as demonstrated by magnetic resonance imaging [MRI] or positron emission tomography [PET]/computed tomography [CT] not older than 4 weeks prior to screening)."}
• {"criterion_text":"- 9. International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a stable dose of anti-coagulant."}

Primary endpoints

• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Safety will be assessed by recording type, frequency and severity of AEs/SAEs, including CRS and ICANS, per standard AE/SAE reporting procedures."}
• {"endpoint_text":"- 2.) Phase I: MTD of SLAMF7 CAR-T that can be administered in phase IIa will be assessed at the end of phase I","definition_or_measurement_approach":"Maximum tolerated dose (MTD) will be determined at end of Phase I based on observed toxicities during dose-escalation cohorts."}
• {"endpoint_text":"- 3.) Phase IIa: Type, frequency, and severity AEs, including SAEs, CRS, and neurotoxicity (i.e. ICANS)","definition_or_measurement_approach":"Safety in Phase IIa assessed by recording AE/SAE incidence, CRS and ICANS occurrences and severity."}
• {"endpoint_text":"- 4.) Phase IIa: Percentage of patients who achieved partial response (PR) or better using the IMWG Uniform Response Criteria for Multiple Myeloma at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 after SLAMF7 CAR-T infusion","definition_or_measurement_approach":"Efficacy measured as percent of patients achieving PR or better according to IMWG Uniform Response Criteria at specified post-infusion timepoints (Months 1,2,3,4,5,6,9,12,15,18,21,24)."}

Secondary endpoints

• {"endpoint_text":"- 1.) Phase IIa: Percentage of patients who achieved CR or better using the IMWG Uniform Response Criteria for Multiple Myeloma at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 after SLAMF7 CAR-T infusion","definition_or_measurement_approach":"Percent achieving complete response (CR) or better by IMWG criteria at specified timepoints."}
• {"endpoint_text":"- 2.) Phase I and IIa: Percentage of myeloma patients enrolled into the trial who receive ex vivo expanded autologous SLAMF7 CAR-T within the 48h shelf-life of the product","definition_or_measurement_approach":"Proportion of enrolled patients who receive product infusion within the defined 48-hour shelf-life window."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Pharmacokinetic/expansion parameters (Cmax, Tmax, AUC) and persistence of CAR-T CD4+ and CD8+ cells measured at listed timepoints."}
• {"endpoint_text":"- 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) Phase I and IIa: Proportion of minimal residual disease (MRD) evaluable patients that are MRD negativ","definition_or_measurement_approach":"Time-to-event measures for response, progression, and death at listed timepoints; MRD negativity proportion assessed in MRD-evaluable patients."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Overall survival measured as time from infusion to death, assessed at listed timepoints."}
• {"endpoint_text":"- 6.) Patient-reported outcomes as measured by EORTC-QLQ-C30/-MY20 at Screening, Baseline, Months 6, 12, 24","definition_or_measurement_approach":"Quality of life assessed via EORTC-QLQ-C30 and QLQ-MY20 questionnaires at listed visits."}

Germany

Earliest CTIS Part Ii Submission Date

16-01-2025

Latest Decision Or Authorization Date

30-01-2025

Processing Time Days

14

Number Of Sites

1

Number Of Participants

33

Primary sponsor

Full Name

Universitaetsklinikum Wuerzburg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Contract research organisations

Name

FGK Clinical Research GmbH

Third parties

• {"country":"Spain","full_name":"Universidad De Navarra","duties_or_roles":"Cytokine analysis, immunophenotyping and MRD by flow cytometry","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Universitaetsklinikum Wuerzburg AöR","duties_or_roles":"Genomic analyses","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}