A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 38
- Locations
- 3
- Primary Endpoint
- Determination of the maximum tolerated dose (MTD) and the recommended phase IIa dose of SLAMF7 CAR-T in patients with MM
Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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
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
- •in first relapse following an autologous stem cell transplantation or
- •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.
- •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.
Arms & Interventions
All eligible patients
Intervention: SLAMF7 CAR-T (Drug)
Outcomes
Primary Outcomes
Determination of the maximum tolerated dose (MTD) and the recommended phase IIa dose of SLAMF7 CAR-T in patients with MM
Time Frame: through study Phase I completion, an average of 2 years
For the primary endpoint in phase I, the maximum tolerated dose will be determined and recommended for phase IIa.
Evaluation of the efficacy, defined as overall response rate (ORR) after treatment with SLAMF7 CAR-T in patients with MM
Time Frame: through study completion, an average of 2 years
In Phase IIa the efficacy will be evaluated, defined as ORR.
Safety determination of the treatment with SLAMF7 CAR-T in phase I
Time Frame: through study completion, an average of 2 years
Type, frequency and severity of AEs in phase I
Safety determination of the treatment with SLAMF7 CAR-T in phases I and IIa
Time Frame: through study completion, an average of 2 years
Type, frequency and severity of AEs in phase I and IIa
Secondary Outcomes
No secondary outcomes reported