| Eligibility |
Inclusion Criteria:
- At least 18 years old (inclusive), gender is not limited;
- Multiple myeloma patients who have received at least 3-line previous multiple myeloma
therapy and have failed at least through proteasome inhibitors and immunomodulators;
Each line of treatment has at least 1 complete treatment cycle, unless the best
remission for the treatment is recorded as disease progression (PD) (according to the
IMWG Efficacy Evaluation Criterialpublished in 2016, Appendix 4); PD must be recorded
during or within 12 months after the last treatment;
- Bone marrow specimens were confirmed by immunohistochemistry or flow cytometry as
positive BCMA expression in plasma cells and myeloma cells (>5%);
- The presence of measurable lesions during screening was defined as any of the
following:
Serum M protein =1 g/dL (=10 g/L); Urinary M protein level =200 mg/24 h; Serum light chain
(FLC) : abnormal serum FLC ratio (< 0.26 or > 1.65), and affected FLC=10 mg/dL (100mg/L);
- ECOG score (Appendix 1) 0~1;
- Expected survival time =3 months;
- The mononuclear cells meet the following standards within 3 days before collection:
Hematology:=0.5×109/L[The use of past granulocyte colony stimulating factor (G-CSF) is
allowed, but patients shall not receive this supportive treatment within 7 days prior to
the screening phase of laboratory examination];=1.0 ×109 /L[Ex-granulocyte
colony-stimulating factor (G-CSF) is allowed, but subjects shall not receive this
supportive treatment within 7 days prior to the screening laboratory examination];Subjects'
platelet count =50×109/L (Subjects shall not receive blood transfusion support within 7
days before the screening laboratory examination);=8.0 g/dL (Recombinant Human
Erythropoietin is allowed) [Subjects have not received a red blood cell infusion (RBC)
within 7 days prior to the screening phase laboratory examination]; Heart:Left ventricular
ejection fraction (LVEF) = 50%; Lung:Blood oxygen saturation =91% under non-inhaled oxygen
condition; Kidney:Creatinine clearance (CRCL) or glomerular filtration rate (GFR)
(Cockcroft-Gault formula) =30 mL/min; Liver:Total bilirubin (serum) =1.5 × ULN;Gilbert's
disease patients with >1.5 × ULN could be enrolled with the consent of the Sponsor; Blood
coagulation:Plasma prothrombin time (PT) =1.5 × ULN, international standardized ratio (INR)
=1.5 × ULN, partial prothrombin time (APTT) =1.5 × ULN;
- Peripheral venous access can meet the needs of single collection and intravenous drip;
- The subject agrees to use reliable contraceptive methods for contraception within 1
year after signing the informed consent form to the infusion. Including but not
limited to: abstinence, men undergoing vasectomy, implantable progesterone
contraceptives that can inhibit ovulation; intrauterine contraceptive devices;
hormone-releasing intrauterine devices; sexual partner sterilization methods; copper
intrauterine devices, Correct use of proven compound hormonal contraceptives that can
inhibit ovulation; progesterone contraceptives that can inhibit ovulation. At the same
time, female subjects should promise not to donate eggs (egg cells, oocytes) for
assisted reproduction within 1 year after the infusion;
- Volunteer to participate in clinical trials and sign Informed Consent Form;
Exclusion Criteria:
- Subjects who are known to have allergic reactions, hypersensitivity, intolerance, or
contraindications to any component of CART-BCMA or any drugs that may be used in the
study (including fludarabine, cyclophosphaamide, or tozumab), or who are allergic to
ß-lactam antibiotics, or who have had severe allergic reactions in the past;
- Prior to any CAR-T therapy or BCMA-targeted therapy;
- Have received the following anti-MM treatment within the prescribed time range before
single calyzer:
Has received small molecule targeted therapy within 4 weeks or 5 half-lives, whichever is
longer; treatment with a large molecule within 4 weeks or 2 half-lives, whichever is
longer; received cytotoxic therapy, proteasome inhibitor, or modern Chinese medicine
preparation with anti-tumor effect within 2 weeks; received immunomodulatory drug therapy
within 1 week; received radiotherapy within 1 week
- Participated in a clinical trial within 4 weeks before the single collection;
- Patients who received autologous hematopoietic stem cell transplantation (ASCT) or
previous allogeneic stem cell transplantation within 12 weeks before a single
collection (no time limit);
- People who received live vaccine or attenuated vaccine within 4 weeks before the
CART-BCMA harvest; Note: Inactivated viral vaccines for seasonal influenza are allowed
for injection; Intranasally administered live attenuated influenza vaccines are not
allowed;
- Received any of the following treatments within 7 days prior to the single collection
or as determined by the investigator to require long-term treatment during the study
period:
Systemic steroid therapy (except inhalation or topical use), Immunosuppressive therapy,
Graft versus host therapy, Preventive treatment of central nervous system
- Incomplete recovery or stabilization to grade 1 (NCI-CTCAE v5.0) of toxicity
(including peripheral neuropathy) caused by previous treatment;
- MM is suspected to be involved in the central nervous system or meninges and confirmed
by MRI or CT, or to have other active central nervous system diseases;
- Patients with plasma cell leukemia or Waldenstrom macroglobulinemia or POEMS syndrome
(polyneuropathy, organ enlargement, endocrine disorder, monoclonal protein, and
cutaneous disease) or amyloidosis at the time of screening;
- Heart disease: Existing heart failure (NYHA classification =II, Appendix 2), unstable
angina pectoris, or severe heart disease as determined by the investigator; Myocardial
infarction had occurred no more than 6 months before single arthroplasty. Had an
episode of unstable angina pectoris, severe arrhythmia as determined by the
researchers, or had undergone coronary artery bypass grafting (CABG) no more than 3
months before the single harvest;
- Poor control of hypertension (systolic blood pressure > 160 mmHg and/or diastolic
blood pressure > 100 mmHg) or with hypertensive crisis or hypertensive encephalopathy;
- Patients who had undergone major surgery or plasma separation other than diagnosis or
biopsy within 4 weeks prior to the study alone, or who were expected to undergo major
surgery during the study period; Note: Patients who plan to undergo surgery under
local anesthesia may participate in the study. Kyphoplasty or vertebra osteoplasty are
not considered major surgery;
- Receiving thrombolytic, anticoagulant or antiplatelet therapy;
- Infections require intravenous antibiotics or hospitalization;
- Patients with active hepatitis B; Hepatitis C virus (HCV) antibody positive;
HIV-positive persons; Syphilis primary screening antibody positive; A)
Inactive/asymptomatic patients with carryable, chronic, or active HBV who meet the
following criteria are eligible for inclusion: HBV DNA <500 IU/mL (or 2500 copies /mL)
at the time of screening.
- Women who are pregnant or lactating;
- The investigator considers that the subject is unsuitable to participate in this
clinical study due to any abnormal clinical or laboratory examination or other
reasons.
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