Trial Title:
To Assess Safety, Tolerability, and Efficacy of Anti-GPRC5D-CD19-CAR-T in Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT06298266
Condition:
Relapsed or Refractory Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
GPRC5D-CD19 CART
Multiple myeloma
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
infusion of GPRC5D-CD19 CAR T injection
Description:
Infusion of GPRC5D-CD19 CAR T cells injection by dose of 1.0×10^6 /kg±20 % CAR-T
，3.0×10^6 /kg±20%、6.0×10^6 /kg±20%. Administration method: intravenous infusion. Subjects
will be treated with Fludarabine and Cyclophosphamide before cell infusion.
Arm group label:
infusion of GPRC5D-CD19 CAR T injection
Summary:
To evaluate the safety and tolerability of anti-GPRC5D-CD19 CAR-T cells infusion in
subjects with relapsed and refractory multiple myeloma
Detailed description:
This study is a single-arm, single-center clinical study of IIT to evaluate the safety,
tolerability, pharmacokinetic profile, and initial efficacy of GPRC5D-CD19 CAR T cells in
subjects with MM. The safety of GPRC5D-CD19 CAR T was evaluated by observing adverse
events after cell therapy. Evaluate the effectiveness of GPRC5D-CD19 CAR T treatment
compared to the results of the subjects' own previous standard treatment regimens or base
data. Blood and bone marrow were collected before and 24 months after the GPRC5D-CD19 CAR
T infusion to detection.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. 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:
-
1. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Second Provincial General Hospital
Address:
City:
Guangzhou
Zip:
510317
Country:
China
Contact:
Last name:
Qing Zhang
Phone:
+862089169186
Email:
zhqing@vip.163.com
Start date:
March 29, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Guangdong Second Provincial General Hospital
Agency class:
Other
Source:
Guangdong Second Provincial General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06298266
