CAR-T Cell Therapy in RelApsed/​Refractory Myeloma With ExtrameduLlary Disease – an in Vivo Imaging and Molecular Monitoring Study (CARAMEL)

NCT 05666700

Brief Summary

Inclusion Criteria

Patients must meet all the following criteria for study entry:

1. Patient has provided written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment.
2. Patient is >18 years of age at the time of consent
3. Patient has a documented diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of MM according to the IMWG diagnostic criteria (Appendix 1)
4. Measurable extramedullary disease by any imaging modality (at least one site of disease ≥1cm that has never received radiotherapy or has progressed following radiotherapy). Presence of biochemical measurable disease is not required
5. Have received at least 2 prior lines of therapy including a PTI and an IMiD. Patient must have undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy (Appendix 2) Note: induction with or without haematopoietic stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells, consolidation and maintenance therapy is considered a single line of therapy.
6. Have an ECOG Performance Status score of 0 or 1 (Appendix 3)
7. Have a life expectancy of ≥3 months, as judged by the Investigator
8. Able to undergo apheresisa medical procedure where a machine separates a particular blood compnent from the blood and then returns the rest to the body for mononuclear cell collection
9. Have clinical laboratory values meeting the following criteria within 7 days prior to registration (enrolment):
   • Haemoglobin ≥80g/L (recombinant human erythropoietin use is permitted)
   • ANC ≥1 × 109/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test)
   • Platelet count ≥50 × 109/L
   • Absolute lymphocyte count ≥0.3 × 109/L
   • AST ≤3.0× ULN
   • ALT ≤3.0× ULN
   • Total bilirubin ≤2.0× ULN; except in patients with congenital bilirubinaemia, such as Gilbert’s syndrome (in which case direct bilirubin ≤2.0× ULN is required)
   • Calculated CrCl ≥40mL/min calculated by the Cockcroft-Gault formula (Appendix 4), nuclear medicinea specialised area of radiology that involves the use of radioactive substances in the diagnosis and treatment of disease assessment or a 24-hour urine collection
10. When a woman is of childbearing potential, the patient must commit either to abstaining continuously from heterosexual intercourse or agree to practice 2 methods of reliable birth control simultaneously. Where one of the methods is highly effective method of contraception (failure rate of <1% per year when used consistently and correctly; see examples below) and one other effective method (i.e., male latex or synthetic condom, diaphragm, or cervical cap) and patient must agree to remain on both methods from the time of signing the PICF until at least 1 year after receiving a cilta-cel infusionto slowly introduce/give fluid into a vein (Appendix 5). Reliable contraception is indicated even where there has been a history of infertility, unless it is due to hysterectomycomplete or partial removal of the uterus. WOCBP should be referred to a qualified provider of contraceptive methods, if needed. Examples of highly effective contraceptives include:
    • User-independent methods: 1) implantable progestogen-only hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone-releasing system; 3) vasectomised partner
    • User-dependent method: progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable)
11. A man must commit either to abstaining continuously from heterosexual intercourse or a man who is sexually active with a WOCBP or a pregnant woman must agree to use a barrier method of contraception (e.g., latex or synthetic condom with spermicidal foam/gel/film/cream/suppository) from the time of signing the PICF until at least 1 year after receiving a cilta-cel, even if they have undergone a successful vasectomy
12. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a cilta-cel infusion
13. Patient must be willing and able to adhere to the following lifestyle restrictions during the study to be eligible for participation:
    • Refer to Section 8.6.3, Prohibited Therapies for details regarding prohibited and restricted therapy during the study
    • Agree to follow all requirements that must be met during the study as noted in the Inclusion and Exclusion Criteria (e.g., contraceptive requirements)