CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Patients \> 18 years old with a diagnosis of post-allogeneic transplant relapse multiple myeloma.
2. Measurable disease at the time of screening
3. Previous treatment with ≥2 lines before and/or after allogeneic transplant.
4. Patients who are not receiving immunosuppressants at least 1 month before inclusion and who do not have active graft-versus-host disease.
5. Eastern Cooperative Oncology Group functional status from 0 to 1.
6. Life expectancy greater than 3 months (at the time of screening)
7. Patients who give their consent by signing the Informed Consent document.

Exclusion Criteria:

1. Active systemic immunosuppressive treatment
2. Patients who have previously received treatment with CAR-T Anti-BCMA.
3. Absolute lymphocyte count \<0.2x109/L
4. Previous neoplasm, except if it has been in complete remission \>3 years, with the exception of skin carcinoma (non-melanoma)
5. Active infection requiring treatment.
6. Active HIV, hepatitis B virus or hepatitis C virus infection.
7. Uncontrolled medical illness.
8. Severe organic disease that meets any of the following criteria: left ventricular ejection fraction \<40%, carbon monoxide diffusion test \<40%, glomerular filtration rate \<50 ml/min, bilirubin \>3 normal value (except Gilbert syndrome).
9. Previous diagnosis of symptomatic amyloid light chain or primary amyloidosis or POEMS Syndrome.
10. Pregnant or lactating women.
11. Women of childbearing age, unable or unwilling to use highly effective contraceptive methods.
12. Men who cannot or do not wish to use highly effective contraceptive methods. The partner of the male participants, if they are women of childbearing age, must also use highly effective contraceptive methods during the study period.
13. Contraindication to receive lymphodepleting chemotherapy.
14. Patients with known hypersensitivity to the active ingredients or any of the excipients of the product to be infused.

主要终点：Purity of CARTemis-1 · Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused · Immediately after infusion；Maximum tolerated dose · To determine the maximum tolerated dose of CarTemis-1 · Up to 30 days；Infusion reactions · To appearance of any of the following symptoms after intravenous administration of CARTemis-1: cardiac events, chills, dyspnea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, skin rash, and urticaria. · Immediately after intravenous administration of CARTemis-1；Tumor lysis syndrome · To increase nucleic acids, potassium, and phosphate in the blood · Up to 30 days after treatment administration；Serious Adverse Event · Type, incidence, severity (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0), timing, intensity, and relatedness of adverse events). · Up to 36 months after treatment administration；Suspected Unexpected Serious Adverse Reaction · Describe the adverse event that occurs in a clinical trial subject, which is assessed by the sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug. · Up to 36 months after treatment administration
次要终点：Number of Participants with cytopenias；Number of Participants with prolonged cytopenias；Duration of clinical response；Overall response rate；Time to complete remission；Time to best response；Negative Minimum Residual Disease Rate；Response rate of extramedullary disease

• CARTemis-1 · EXPERIMENTAL · Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered.

Most patients with multiple myeloma (MM) die due to relapse resistant to current treatment, including treatment with anti-B cell maturation antigen (BCMA) CAR-T cells. To overcome some of the potential limitations of this therapy, a new and optimized Anti-BCMA CAR-T has been developed, with the aim of using it in patients with MM who relapse after Allogeneic Haematopoietic Haematopoietic Progenitor. This trial is a prospective phase I/II trial with a 3+3 design. Once Dose Limiting Toxicity is identified, Phase II will begin to assess the efficacy of the procedure.