A Study of VRd-based Regimen Combined With CART-ASCT-CART2 Treatment in NDMM Patients With P53 Abnormalities

Study Purpose

This is a single-arm, open-label study to evaluate the efficacy and safety of VRD(Bortezomib, Lenalidomide and Dexamethasone)-based regimen combined with CART-ASCT-CART2 in patients with newly diagnosed multiple myeloma with p53 gene abnormalities.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 65 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Willing and able to give written informed consent (ICF) . 2. Age ≥ 18 years and ≤ 65 years. 3. Meet the internationally accepted Criteria for the diagnosis of newly diagnosed multiple myeloma (Chinese guidelines for the diagnosis and management of multiple myeloma (revised in 2022) criteria) 4. Patients have not received previous anti-multiple myeloma-related chemotherapy, have not received previous extensive pelvic radiotherapy (more than half of the pelvic area), and have not received previous anti-multiple myeloma hormone therapy, except for those who have used hormones for no more than 14 days for symptom control. 5. The patient have one or more measurable multiple myeloma lesion, must include one of the following conditions:
  • - Serum M protein≥1.0 g/dL(10g/L) - Urine M protein≥200 mg/24h.
  • - Serum free light chain(sFLC): κ/λ FLC ratio is abnormal and affected FLC ≥10mg / dL.
6. p53 gene abnormalities: Plasma cells were enriched by CD138 immunomagnetic and then detected by FISH. Cut-off ≥20%., or P53 mutation by second-generation sequencing. 7. ECOG scores 0
  • - 1; 8.
No active infection. 9. All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria: a.TBIL<1.5 x upper limit of normal (ULN) (<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT <3 x ULN.; c. Creatinine clearance ≥ 60mL/min (calculated using Cockroft-Gault formula). 10. normal pulmonary function and oxygen saturation ≥ 92% on room air. 11. Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 85 g/L PLY ≥ 75 x 109/L (if BMPC < 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%) 12. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 13. The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter. 14. Willing and able to complete the study procedures and follow-up examinations.

Exclusion Criteria:

1. Plasma cell leukemia. 2. Documented active amyloidosis. 3. Multiple myeloma with central nervous system (CNS) invasion. 4. Unsuitable for autologous stem cell transplantation, such as severe cardiopulmonary disorders. 5. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy. 6. Known intolerance, hypersensitivity, or contraindication to BCMA-CART cellular products. 7. Patients with unstable or active cardiovascular system disease, meeting any of the following: 1. Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarction or coronary artery reconstruction within 180 days prior to the first dose. 2. Uncontrolled hypertension (>140/90 mmHg with blood pressure fluctuations of more than 180/100 mmHg over a 6-month period). 3. Uncontrolled and clinically significant conduction abnormalities (e.g. patients with ventricular arrhythmias controlled by antiarrhythmic medication), not excluding patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior bundle branch block/right bundle branch block (LAFB/RBBB)). 4. Congestive heart failure (CHF) classification ≥ grade 3 as defined by the New York Heart Association (NYHA). 5. Left ventricular ejection fraction (LVEF) <50% on echocardiography. 6. History of stroke or intracranial haemorrhage within 12 months prior to screening. 7. Presence of a serious thrombotic event prior to treatment. 8. Known positive serology for HIV or HIV seropositivity. 9. Active hepatitis B or C infection. Screening requires serologic testing for hepatitis. If hepatitis B surface antigen and hepatitis B core antibody were positive, a negative DNA polymerase chain reaction (PCR) result was needed before enrollment (after anti-hepatitis B therapy, a negative DNA polymerase PCR result was confirmed before enrollment). If the hepatitis C antibody was positive, the RNA PCR test should be negative prior to enrollment. 10. Life expectancy of <3 months. 11. Women who are pregnant or breastfeeding. 12. Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect the absorption of the studied treatment medication. 13. Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or is not fully recovered from the surgery, or surgery is arranged during study period. 14. Received live attenuated vaccine within 4 weeks prior to study treatment. 15. According to the researcher's judgement, any condition including but not limited to serious mental illness, medical illness or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent. 16. Necessary medication or supportive therapy is contraindicated with study treatment. 17. Any diseases or complications that may interfere with the study. 18. Patients are not willing to or cannot comply with study scheme.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05850286
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Institute of Hematology & Blood Diseases Hospital, China
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of treatment with the VRd (short for Bortezomib, Lenalidomide, Dexamethasone)-based regimen in combination with the CART-ASCT-CART2 in newly diagnosed multiple myeloma patients with P53 gene abnormalities. Patients received 3 courses of induction therapy with VRd-based regimen followed by a first infusion of CAR-T cells. Patients then received 3 courses of consolidation therapy, followed by ASCT and second infusion of CAR-T cells. R maintenance therapy starts on day 100 after ASCT

Arms & Interventions

Arms

Experimental: VRD-based Regimen Combined With CART-ASCT-CART2

Autologous BCMA-directed CAR-T cells, Double infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg respectively. Participants will receive VRD-based regimen induction, first CAR-T infusion, consolidation, ASCT and second CAR-T infusion. Maintenance therapy was initiated on day 100 and entered the follow-up period.

Interventions

Biological: - anti-BCMA CAR-T

Autologous BCMA-directed CAR-T cells, double infusion intravenously at a target dose of 2.0-4.0 x 10^6 anti-BCMA CAR+T cells/kg.

Drug: - VRD-based Regimen

Bortezomib, Lenalidomide and Dexamethasone

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Tianjin, China

Status

Recruiting

Address

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, ,

Site Contact

Gang An, PhD&MD

angang@ihcams.ac.cn

008613502181109