KOALA: Testing a new CAR T-cell therapy in people with relapsed or refractory multiple myeloma that expresses KMAA Phase I Study of Autologous Chimeric Antigen Receptor (CAR) T-cells Targeting the Kappa Myeloma Antigen (KMA) in Kappa Restricted Multiple Myeloma Patients With Relapsed/Refractory Disease

Inclusion

1. Patient has provided written informed consent using the KOALA Patient Information and Consent Form (PICF)
2. Age ≥ 18 years on the day of signing informed consent form
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2 (Appendix 2)
4. Life expectancy of ≥ 3 months, as assessed by the Investigator
5. A diagnosis of kappa-restricted RR MM with evidence of KMA on the surface of bone marrow plasma cells using flow cytometry analysis as determined by investigator
6. Have received at least 2 prior lines of therapy including a proteosome inhibitor and an immunomodulatory imide drug with evidence of disease progression as per IMWG criteria (Appendix 1) after the most recent line of therapy Note 1: induction with or without haematopoietic stem cell transplant (SCT), consolidation and maintenance therapy is considered a single line of therapy Note 2: Patients who have had prior treatment with a CAR T-cell therapy are eligible after a minimum of a 12 week washout between infusions.
7. Have measurable disease as defined by: • Serum IgG, IgA, IgM M protein ≥ 0.5 g/dL; or • Serum IgD M protein ≥ 0.05 g/dL; or • An abnormal free light chain (FLC) assay (Freelite™) demonstrating an excess of kFLC with a kFLC component of at least 100 mg/L and an abnormal k:λ FLC ratio Note: Patients who do not have measurable disease but who have demonstrable disease (i.e., oligo-secretory myeloma) based on evidence of bone lesions by at least 2 prior PET scan studies showing persistent disease may be included
8. Last dose of nitrosourea, nitrogen mustards, or monoclonal antibody must have been at least 4 weeks prior to registration; autologous SCT must have been at least 12 weeks prior to registration; and allogeneic SCT must have been at least 24 weeks prior to registration. Limited field radiotherapy to painful lesions is allowed during Screening and bridging but must be completed 48 hours prior to planned apheresis and lymphodepleting chemotherapy
9. Adequate haematological function documented within 7 days prior to registration, defined as: • Haemoglobin ≥ 80 g/L (peripheral red blood cell transfusion support is allowed if marrow infiltrate is ≥ 50%) • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (GCSF support is allowed) , and ANC > 0.5 x 109/L is allowed if neutropenia is due to disease infiltration of bone marrow) • Absolute lymphocyte count (ALC) ≥ 0.1 x 109/L • Platelets ≥ 50 x 109/L (platelet transfusion support is allowed for platelets ≥ 30 if due to disease infiltration by bone marrow, or splenomegaly due to disease involvement)
10. Adequate cardiac function, defined as: • Left ventricular ejection fraction (LVEF) ≥ 40% on echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 90 days prior to registration• No suspicion for intercurrent deterioration in left ventricular function as assessed by the Investigator
11. Adequate pulmonary function, defined as: • Oxygen saturation measured by pulse oximetry ≥ 90% on room air
12. Adequate renal function documented within 7 days prior to registration, defined as any one of: • A serum creatinine ≤ 1.5 x upper limit of normal (ULN) • Creatinine clearance (CrCl) of ≥ 40 mL/min calculated by Cockcroft-Gault formula (Appendix 3) • CrCl ≥ 40 mL/min calculated by 24-hour urine collection post-ovulation methods) and withdrawal are not acceptable • Glomerular filtration rate (GFR) ≥ 40 mL/min by renal scintigraphy
13. Adequate hepatic function documented within 7 days prior to registration, defined as all of: • Total bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN in patients with Gilbert's syndrome or documented liver involvement) • Alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in patients with documented liver involvement) • Aspartate aminotransferase (AST) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in patients with documented liver involvement)
14. Taking a maximum corticosteroid dose of 20 mg of oral prednisone or equivalent
15. Females of childbearing potential (FCBP) and nonsterile male patients (with partners of childbearing potential) must agree to use highly effective methods of contraception from registration on the study to 2 months after the PMCC-COE-KMA infusion or until PMCC-COE-KMA CAR T-cells are no longer present by quantitative PCR on 2 consecutive tests whichever is later. Effective methods of contraception are: • Total abstinence from sexual intercourse when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptablemethods of contraception • Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least 6 weeks prior to registration. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by followup hormone level assessment • Male sterilisation (at least 6 months prior to Screening), noting that for female patients on the study, the vasectomised male partner should be the sole partner for that patient • Use of oral, (oestrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months prior to registration • Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., ageappropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks prior to registration. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential
16. Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test within 3 days prior to registration
17. Sexually active male patients must use a condom during intercourse and must agree to refrain from sperm donation, from registration on the study until 52 weeks after the PMCC-COE-KMA infusion