A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in-human clinical trial of adoptive immunotherapy with autologous signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR)-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in human clinical trial of adoptive immunotherapy with autologous SLAMF7 CAR-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
SLAMF7 CAR-T cells are manufactured using virus-free gene-transfer using the Sleeping Beauty transposon system.
The CAR-T cell product is formulated to contain equal proportions of CD8 cytotoxic and CD4 helper SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Inclusion Criteria:
Signed informed consent form.
Patient is ≥18 years of age.
Patient is willing and able to adhere to the protocol requirements.
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).
At least one of the following subcriteria must be measured in the patient:
Patients previously treated with an anti-SLAMF7 antibody are eligible.
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.
Female patients of childbearing potential must:
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:
Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤12 months prior to leukapheresis.
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.
Patient with diagnosis of MM
Patient has received anti-CD38 and/or anti-SLAMF7 antibodies ≤8 weeks prior to leukapheresis.
Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or systemic steroids at any dose).
(Note: Physiologic steroid replacement therapy, topical immune-suppressants as e.g. cyclosporine/tacrolimus eye drops and topical steroids are permitted.)
Echocardiogram with left ventricular ejection fraction <45%.
Inadequate renal function defined by creatinine clearance (CrCl) ≤45 mL/min using Cockcroft-Gault equation.
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 MRI or positron emission tomography (PET)/computed tomography (CT) not older than 4 weeks prior to screening).
International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a stable dose of anti-coagulant.
Evidence of human immunodeficiency virus (HIV) infection.
Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV), excluding
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 RNA for 6 months.
Seropositive for syphilis on treponema pallidum hemagglutination test, excluding
- Patients with negative treponema pallidum antibody absorption test result
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.
Pregnant or lactating women.
Current or previous (within 30 days of enrollment) treatment with another IMP.
Known abuse of alcohol, drugs, or medicinal products.
Employees of the sponsor, or employees or relatives of the investigator.