Multiple Myeloma in RelapsePhase 1/2NCT05749133
Safety and Efficacy of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM
A Phase 1/2 study testing Anti-GPRC5D CAR-T Cells Injection in people with Multiple Myeloma in Relapse and Multiple Myeloma, Refractory, run by XuYan at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma in Relapse, Multiple Myeloma, Refractory
- What is being tested?
- Anti-GPRC5D CAR-T Cells Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 10 Apr 2023to Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure.
- Age 18 to 75 years old, gender is not limited.
- Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
- Have received third-line or above treatment.
- 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.
- 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).
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- Eastern cooperative oncology group (ECOG) score is 0-2, and survival is expected to be greater than 3 months.
- 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.
- The venous access required for collection can be established, and there are no contraindications to leukocyte collection.
Who cannot join
- Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma within 3 years.
- 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%).
- 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.
- Patients with macroglobulinemia, POEMS syndrome (polyneuropathy, organ enlargement, endocrine disease, monoclonal proteinosis, and skin changes) or primary AL amyloidosis at the time of screening.
- 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.
- 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.
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- 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.
- Systemic diseases judged by investigators to be unstable, including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment.
- Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months prior to screening, or requiring immunosuppressive therapy for GVHD.
- 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)).
- 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.
- The presence of an uncontrolled bacterial, fungal, viral or other infection requiring antibiotic treatment.
- 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.
- Those who have received (attenuated) live virus vaccine within 4 weeks before screening.
- Persons with severe mental illness.
- Those who are alcoholics or have a history of drug abuse.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of Hematology & Blood Diseases Hospital
Tianjin
Yan Xu, MD, 13920593907, xuyan1@ihcams.ac.cn
About this study
Official title: An Investigator-initiated Trial Evaluating the Efficacy and Safety of Anti-GPRC5D CAR-T Cells Therapy in Patients With Relapsed / Refractory(r/r) Multiple Myeloma(MM) Who Have Received Third-line or More Treatments
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.
Read the 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.
- Being tested
- Anti-GPRC5D CAR-T Cells Injection
- Keywords
- CAR-T
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-GPRC5D CAR-T Cells InjectionBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Anti-GPRC5D CAR-T | Experimental | Subjects who meet the enrollment conditions will receive intravenous infusion of Anti-GPRC5D CAR-T Cells Injection, doses of 1.0~6.0×10^6 /kg±20% CAR-T cells, after lymphodepleting therapy. Receives: Biological: Anti-GPRC5D CAR-T Cells Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events(AE) after infusion
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Measured: Up to the subject withdrew or 24 months after CAR-T infusion.
Dose limited toxicity (DLT)
Dose limited toxicity(DLT) was defined as the occurrence of any of the following adverse events within 28 days of the infusion of CAR-T cells after optimal supportive treatment, which were discussed with the investigator and determined to be associated or likely to be associated with the infusion.
Measured: Up to 28 days after infusion.
Overall response rate(ORR)
Overall Response Rate (ORR) is defined as the proportion of subjects achieving strict complete remission(sCR), complete response(CR), very good partial response(VGPR) and partial response(PR).
Measured: Day 28 and months 3, 6, 9, 12, 18, 24 after CAR-T infusion.
Clinical benefit rate
It's defined as the sum of the proportion of subjects who achieved ORR (sCR + CR + VGPR + PR) and minimal response (MR) according to the International Myeloma Working Group (IMWG) criteria.
Measured: Day 28 and months 3, 6, 9, 12, 18, 24 after CAR-T infusion.
Progression-free survival(PFS)
Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause.
Measured: Up to 24 months after CAR-T infusion.
Overall survival(OS)
Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause).
Measured: Up to 24 months after CAR-T infusion.
Secondary outcomes (2)
Concentration of CAR-T cells
Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion.
Measured: Up to 3 months after CAR-T infusion.
Concentration of cytokine
Concentration of CAR-T cells measured by ELISA or other methods after CAR-T infusion.
Measured: Up to 28 days after CAR-T infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2023
- Study start10 Apr 2023
- Primary completionMar 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Myeloma in RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- XuYan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, XuYan, Institute of Hematology & Blood Diseases Hospital, China
- Investigators
- Yan Xu, MD, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05749133
- Sponsor's protocol ID
- BG-CT-22-011
- Status last verified
- Apr 2023
- First submitted
- 18 Feb 2023
- Last updated
- 20 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-initiated Trial Evaluating the Efficacy and Safety of Anti-GPRC5D CAR-T Cells Therapy in Patients With Relapsed / Refractory(r/r) Multiple Myeloma(MM) Who Have Received Third-line or More Treatments
- ClinicalTrials.gov ID
- NCT05749133
- Acronym / sponsor ID
- BG-CT-22-011
- Keywords
- CAR-T
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- XuYanUniversity, hospital or other
- Study start
- 10 Apr 2023 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 1 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-GPRC5D CAR-T | Experimental | Biological: Anti-GPRC5D CAR-T Cells InjectionSubjects who meet the enrollment conditions will receive intravenous infusion of Anti-GPRC5D CAR-T Cells Injection, doses of 1.0~6.0×10^6 /kg±20% CAR-T cells, after lymphodepleting therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- The patient understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure.
- Age 18 to 75 years old, gender is not limited.
- Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
- Have received third-line or above treatment.
- 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.
Key exclusion criteria (18 listed)
- Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma within 3 years.
- 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%).
- 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.
- Patients with macroglobulinemia, POEMS syndrome (polyneuropathy, organ enlargement, endocrine disease, monoclonal proteinosis, and skin changes) or primary AL amyloidosis at the time of screening.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-GPRC5D CAR-T Cells InjectionThis 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. | Biological | Anti-GPRC5D CAR-T |
Primary outcome
Incidence of adverse events(AE) after infusion
Time frame: Up to the subject withdrew or 24 months after CAR-T infusion.
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Dose limited toxicity (DLT)
Time frame: Up to 28 days after infusion.
Dose limited toxicity(DLT) was defined as the occurrence of any of the following adverse events within 28 days of the infusion of CAR-T cells after optimal supportive treatment, which were discussed with the investigator and determined to be associated or likely to be associated with the infusion.
Overall response rate(ORR)
Time frame: Day 28 and months 3, 6, 9, 12, 18, 24 after CAR-T infusion.
Overall Response Rate (ORR) is defined as the proportion of subjects achieving strict complete remission(sCR), complete response(CR), very good partial response(VGPR) and partial response(PR).
Clinical benefit rate
Time frame: Day 28 and months 3, 6, 9, 12, 18, 24 after CAR-T infusion.
It's defined as the sum of the proportion of subjects who achieved ORR (sCR + CR + VGPR + PR) and minimal response (MR) according to the International Myeloma Working Group (IMWG) criteria.
Progression-free survival(PFS)
Time frame: Up to 24 months after CAR-T infusion.
Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause.
Overall survival(OS)
Time frame: Up to 24 months after CAR-T infusion.
Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause).
2 secondary outcomes
Concentration of CAR-T cells
Time frame: Up to 3 months after CAR-T infusion.
Concentration of cytokine
Time frame: Up to 28 days after CAR-T infusion.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yan Xu, MD principal investigator
Institute of Hematology & Blood Diseases Hospital, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anti-GPRC5D CAR-T Cells Injection in people with Multiple Myeloma in Relapse and Multiple Myeloma, Refractory, run by XuYan at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yan Xu, MD (13920593907 ext. +86, xuyan1@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events(AE) after infusion (time frame: Up to the subject withdrew or 24 months after CAR-T infusion.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2023.