Inclusion Criteria:
The patient or their legal guardian understands and voluntarily signs the informed
consent form and is expected to complete the follow-up examinations and treatments.
2. Age between 18-75 years, regardless of gender. 3. Diagnosed with multiple myeloma
according to the IMWG diagnostic criteria, and GPRC5D expression in bone marrow is
positive (>10%).
4. Has failed treatment with at least three different mechanisms of drugs (including
chemotherapy, proteasome inhibitors, immune modulators, etc.), or has experienced
disease progression or relapse within 6 months after the last treatment.
5. Measurable lesions are present based on any of the following criteria during
screening:
- (1) Serum monoclonal immunoglobulin (M-protein) level ≥1.0 g/dL; (2) Urine
M-protein level ≥200 mg/24 hours; (3) Diagnosed with light chain multiple myeloma with
no measurable lesions in serum or urine: Serum free light chain ≥10 mg/dL and abnormal
serum free light chain κ/γ ratio.
6. The patient has recovered from toxicities associated with previous treatment, i.e.,
CTCAE toxicity grade <2 (unless the abnormality is related to the tumor or stable,
with no significant impact on safety or efficacy as determined by the investigator).
7. ECOG performance status of 0-2 and an expected survival of more than 3 months.
8. Adequate organ function:
- - Alanine transaminase (ALT) ≤3 times the upper limit of normal (ULN);
- Aspartate transaminase (AST) ≤3 times ULN;
- Total bilirubin ≤1.5 times ULN;
- Serum creatinine ≤1.5 times ULN, or creatinine clearance ≥60 mL/min;
- Indoor oxygen saturation ≥92%;
- Left ventricular ejection fraction (LVEF) ≥45%, confirmed by echocardiography with no
clinically significant pericardial effusion or clinically significant
electrocardiogram findings;
- No clinically significant pleural effusion.
9. Able to establish the required venous
access for sample collection, with no contraindications for white blood cell
collection.
Exclusion Criteria:
Diagnosed with or treated for invasive malignant tumors other than multiple
myeloma.
2. Previously received anti-tumor treatments including targeted therapy, epigenetic
therapy, experimental drug therapy, or invasive experimental medical devices within 14
days or at least 5 half-lives (whichever is shorter) before the collection and
preparation of CAR-T cells. Also, received monoclonal antibody therapy for
relapsed/refractory multiple myeloma within 21 days, received cytotoxic therapy within
14 days, received proteasome inhibitor therapy within 14 days, received
immunomodulatory agent therapy within 7 days, or received radiation therapy within 14
days (except for bone marrow reserves with field coverage ≤5%).
3. Suspected involvement of multiple myeloma in the central nervous system or meninges
confirmed by MRI or CT, or presence of other active central nervous system diseases.
4. Screening criteria include plasma cell leukemia (according to standard
classification, plasma cells >2.0×109/L), Waldenstrom macroglobulinemia, POEMS
syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin
changes), or secondary AL amyloidosis.
5. Positive for hepatitis B surface antigen (HBsAg) and positive for HBV-DNA; positive
for hepatitis C virus (HCV) antibody; positive for human immunodeficiency virus (HIV)
antibody; cytomegalovirus (CMV) DNA test result ≥500 copies/mL; positive for syphilis
test.
6. Positive for hepatitis C virus (HCV) antibody; positive for human immunodeficiency
virus (HIV) antibody; cytomegalovirus (CMV) DNA test result ≥500 copies/mL; positive
for syphilis test.
7. History of severe allergies defined as grade II or above reactions, with clinical
manifestations including airway obstruction (runny nose, coughing, wheezing,
difficulty breathing), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms
(nausea, vomiting), urinary or fecal incontinence, laryngeal edema, bronchospasm,
cyanosis, shock, respiratory or cardiac arrest, or known allergy to any active
ingredient, excipient, murine-derived product, or xenogeneic protein contained in this
trial (including the CleenRx regimen).
8. Severe cardiac diseases including but not limited to severe arrhythmias, unstable
angina pectoris, extensive myocardial infarction, New York Heart Association Class III
or IV heart failure, myocardial infarction within 6 months before screening or
coronary artery bypass graft (CABG), unexplained history of syncope unrelated to
vasovagal or dehydration, severe non-ischemic cardiomyopathy, or uncontrolled
hypertension (defined as failure to achieve blood pressure goals despite using ≥3
antihypertensive drugs, including diuretics, for ≥1 month or effective blood pressure
control requiring ≥4 antihypertensive drugs).
9. Unstable systemic diseases, including but not limited to severe liver, kidney, or
metabolic diseases requiring medication.
10. Acute/chronic graft-versus-host disease (GVHD) within 6 months before screening or
patients requiring immunosuppressive therapy for GVHD.
11. Active autoimmune or inflammatory diseases of the nervous system (e.g.,
Guillain-Barré syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically
significant active cerebrovascular diseases (e.g., cerebral edema, posterior
reversible encephalopathy syndrome (PRES)).
12. Presence of tumor emergencies (e.g., spinal cord compression, intestinal
obstruction, leukostasis, tumor lysis syndrome) requiring urgent treatment during
screening or before cell infusion.
13. Uncontrolled bacterial, fungal, viral, or other infections requiring antibiotic
treatment.
14. Underwent major surgery (excluding diagnostic surgery and biopsies) within 4 weeks
before CleenRx or planned major surgery during the study, or incomplete healing of
surgical wounds before enrollment.
15. Received (attenuated) live virus vaccines within 4 weeks before screening. 16.
Presence of severe mental disorders. 17. Alcohol or substance abuse history. 18.
Pregnant or breastfeeding women, and female subjects or male subjects with partners
planning pregnancy within 2 years after cell infusion, and subjects who plan to become
pregnant within 2 years after cell infusion. Additionally, according to the
investigator's judgment and/or clinical criteria, patients with contraindications to
any study procedures or other medical conditions that may expose them to unacceptable
risks.
