The CARAMBA Project
A clinical proof-of-concept for CAR-T cells has already been obtained in other hematological malignancies, e.g. B cell leukemia and lymphoma, resulting in dramatic and durable anti-tumour responses in patients. CARAMBA will be the first clinical trial to target the myeloma-specific protein SLAMF7. The project has a mission to better understand the role of CAR-T therapy in myeloma and to explore regulatory and sustainable funding approaches for health care systems to ensure patients can access this type of innovation.
Cutting-edge CAR technology – made in the EU
Chimeric antigen receptors (CARs) are synthetic designer molecules that are capable of redirecting the specificity of T cells to potently eliminate tumour cells. We have now developed a novel and unique CAR approach targeting the SLAMF7 antigen in myeloma and already obtained proof-of-efficacy in comprehensive preclinical testing.
A major achievement in the CAR-T design has been accomplished through our expertise in “Sleeping Beauty” transposition (i.e. the delivery of the CAR engineered gene into the human cells). In CAR-T this is typically done using viral systems or “vectors” which are efficient but may pose risks to the patient. Our approach guarantees a viral-free, high-level CAR gene transfer into safe genomic loci and is a major milestone for the development of a myeloma CAR therapy.
The manufacturing process for CAR-T cells using our novel Sleeping Beauty-based gene-transfer approach has already been established under good manufacturing practice (GMP) conditions ensuring a rapid and high-quality production process.
SLAMF7 CAR-T clinical trial – 4 sites 30 patients
The clinical trial within CARAMBA is designed as a Phase I/II trial. Phase I is a dose escalation study and will explore the effective dose of the CAR-T cell product. For the Phase II part of the trial, 25 patients will be treated with the maximum tolerated dose of SLAMF7 CAR-T. After CAR-T cell infusion, all patients will be observed as inpatients (in hospital) for at least one week and then periodically as outpatients (at home).
For the treatment the process is as follows:
- A patient’s white blood cells are extracted by leukapheresis
- The white blood cells are then separated to identify appropriate T-Cells (immune cells) to undergo adaptation for CAR-T
- “CAR” gene sequences are inserted into the DNA of the T cells to create the “CAR-T cells”. This engineers them to be able to find and target the SLAMF7 protein on myeloma cells.
- The modified T cells are then expanded ex-vivo (outside the body)
- Subsequently, T cells are infused back into the patients, where they can multiply when they encounter the targeted proteins and kill the targeted cancer cell.
Universitaetsklinikum Wuerzburg (Wuerzburg, Germany)
Universidad de Navarra (Pamplona, Spain)
Ospedale San Raffaele (Milano, Italy)
Centre Hospitalier Regional et Universitaire de Lille (Lille, France)
CARAMBA is a EU-funded project that has started on 1st January 2018 with a project period of 52 months. Within its first 18 months, the GMP manufacturing process of the CAR-T product as well as the clinical trial approval will be finalized. We are confident that the first phase I patients will be recruited in summer 2019 and patients for phase II will be screened from summer 2020 onwards. CARAMBA is highly committed to an open data policy and will present its generated data after completion of phase I (beginning of 2020) and II (summer 2022) at national and international meetings to physicians and the patients’ community.