Trial Title:
Safety and Efficacy of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM
NCT ID:
NCT05749133
Condition:
Multiple Myeloma in Relapse
Multiple Myeloma, Refractory
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
CAR-T
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Anti-GPRC5D CAR-T Cells Injection
Description:
This is a"3+3"dose escalation study, in which three dose groups are set three different
dose levels of CAR-T cells: Initial dose group: 3.0×10^6/kg±20%; Low dose group:
3.0×10^6/kg±20%; High dose group: 6.0×10^6/kg±20%. Dose was weight-based.
Arm group label:
Anti-GPRC5D CAR-T
Summary:
It is a single-center, open-labeled, single-arm, non-randomized investigatorinitiated
trial evaluating the efficacy and safety of anti-GPRC5D CAR-T cells therapy for relapsed
and refractory(r/r) multiple myeloma(MM) after three or more lines of treatments.
Detailed description:
This open label, single-arm, investigator-initiated study aims to evaluate the efficacy
and safety of Anti-GPRC5D CAR-T in subjects with relapsed and refractory(r/r) multiple
myeloma(MM) after three or more lines of treatments. A leukapheresis procedure will be
performed to manufacture Anti-GPRC5D chimeric antigen receptor (CAR) modified T cells.
Prior to Anti-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy
with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T
therapy was evaluated by investigators.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient understands and voluntarily signs the informed consent, and is expected
to complete the follow-up examination and treatment of the study procedure.
2. Age 18 to 75 years old, gender is not limited.
3. Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
4. Have received third-line or above treatment.
5. Have measurable lesions at screening period, defined as any of the following : (1)
serum monoclonal immunoglobulin (M-protein) level ≥1.0 g/dL. (2) urine M protein
level ≥200 mg/ 24h. (3) Light chain multiple myeloma diagnosed with no measurable
lesion in serum or urine: serum immunoglobulin free light chain is ≥10 mg/dL and
serum immunoglobulin κ/γ free light chain ratio is abnormal.
6. The patient has recovered from the toxicity of the previous treatment, that is, the
CTCAE toxicity grade is less than 2 (unless the abnormality is related to the tumor
or is in a stable state as judged by the investigator, which has little effect on
safety or efficacy).
7. Eastern cooperative oncology group (ECOG) score is 0-2, and survival is expected to
be greater than 3 months.
8. Has proper organ function: (1) Alanine aminotransferase (ALT) ≤3 times the upper
limit of normal (ULN). (2) Aspartate aminotransferase (AST) ≤3 times ULN. (3) Total
bilirubin ≤1.5 ULN. (4) Serum creatinine ≤1.5 ULN, or creatinine clearance ≥60
mL/min. (5) Indoor oxygen saturation ≥92%. (6) Left ventricular ejection fraction
(LVEF) ≥45%, echocardiography confirmed no pericardial effusion, no ECG findings
with clinical sense. (6) There was no clinically significant pleural effusion.
9. The venous access required for collection can be established, and there are no
contraindications to leukocyte collection.
Exclusion Criteria:
1. Have been diagnosed with or treated for aggressive malignancies other than multiple
myeloma within 3 years.
2. Subjects who have received the following therapies before blood collection: have
received targeted therapy, epigenetic therapy, or investigational drug therapy or
invasive investigational medical device within 14 days or at least five half-lives,
whichever is shorter, or have treated with monoclonal antibodies within 21 days, or
have received cytotoxic therapy within 14 days, or have treated with a proteasome
inhibitor within 14 days, or have treated with an immunomodulatory agent within 7
days, or have received radiotherapy within 14 days (except bone marrow reserve with
field coverage ≤ 5%).
3. It is suspected that MM has involved the central nervous system or meninges and has
been confirmed by MRI or CT, or there are other active central nervous system
diseases.
4. Patients with macroglobulinemia, POEMS syndrome (polyneuropathy, organ enlargement,
endocrine disease, monoclonal proteinosis, and skin changes) or primary AL
amyloidosis at the time of screening.
5. Hepatitis B surface antigen (HBsAg) is positive, or Hepatitis B core antibody
(HBcAb) positive while HBV DNA titer in peripheral blood higher than the lower limit
of detection. Hepatitis C virus (HCV) antibody positive and the peripheral blood HCV
RNA also positive. Human immunodeficiency virus (HIV) antibody positive.
Cytomegalovirus (CMV) DNA test results ≥500 copies /mL. Syphilis test positive.
6. Those with a history of severe allergies or known any of the active ingredients,
excipients or mouse-derived products contained in the drug, or those allergic to
xenogeneic proteins in this trial, including lymphocyte depletion regimens. Severe
allergy history is defined as an allergic reaction of grade two or above, and any of
the following clinical manifestations occur when an allergic reaction occurs: airway
obstruction (runny nose, cough, wheezing, dyspnea), hypercardia tachycardia,
hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence,
laryngeal edema, bronchospasm, cyanosis, shock, respiration, cardiac arrest.
7. Severe heart disease, including but not limited to severe arrhythmia, unstable
angina, massive myocardial infarction, New York Heart Association class III or IV
cardiac insufficiency, refractory hypertension (refractory Hypertension is defined
as: on the basis of improving lifestyle, a reasonable tolerable and sufficient
amount of ≥3 kinds of antihypertensive drugs (including diuretics) has been used for
> 1 month and the blood pressure has not reached the standard, or the blood pressure
can only be achieved effective control after taking ≥4 kinds of antihypertensive
drugs.
8. Systemic diseases judged by investigators to be unstable, including but not limited
to severe liver, kidney or metabolic diseases requiring drug treatment.
9. Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months prior
to screening, or requiring immunosuppressive therapy for GVHD.
10. Active autoimmune or inflammatory diseases of the nervous system (eg, Guillain-Barre
syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant
active cerebrovascular disease (eg, cerebral edema) , Posterior Reversible
Encephalopathy Syndrome (PRES)).
11. Those who have tumor emergencies (such as spinal cord compression, intestinal
obstruction, leukostasis, tumor lysis syndrome, etc.) before screening or reinfusion
and need emergency treatment.
12. The presence of an uncontrolled bacterial, fungal, viral or other infection
requiring antibiotic treatment.
13. Those who have undergone major surgical operations (except diagnostic surgery and
biopsy) within 4 weeks before clearing the lymph cells, or those who plan to undergo
major surgery during the study period, or those whose surgical wounds have not
healed completely before enrollment.
14. Those who have received (attenuated) live virus vaccine within 4 weeks before
screening.
15. Persons with severe mental illness.
16. Those who are alcoholics or have a history of drug abuse.
17. Pregnant or lactating women, female subjects who plan to have a pregnancy within 2
years after cell infusion, and male subjects whose partners plan to have a pregnancy
within 2 years after cell infusion.
18. Patients who are contraindicated with any study procedure or have other medical
conditions that may expose them to unacceptable risks in accordance with the
investigator's judgment and/or clinical standards. 19. Patients who, in the judgment
of the investigator and/or clinical standards, are contraindicated with any study
procedure or have 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:
Institute of Hematology & Blood Diseases Hospital
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Contact:
Last name:
Yan Xu, MD
Phone:
13920593907
Email:
xuyan1@ihcams.ac.cn
Start date:
April 10, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
XuYan
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05749133
