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

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

NCT ID: NCT05850286

Condition: Multiple Myeloma

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell

Study type: Interventional

Study phase: 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-BCMA CAR-T
Description: 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.
Arm group label: VRD-based Regimen Combined With CART-ASCT-CART2

Intervention type: Drug
Intervention name: VRD-based Regimen
Description: Bortezomib, Lenalidomide and Dexamethasone
Arm group label: VRD-based Regimen Combined With CART-ASCT-CART2

Summary: 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.

Detailed description: 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

Criteria for eligibility:
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.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Locations:

Facility:
Name: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Address:
City: Tianjin
Country: China

Status: Recruiting

Contact:
Last name: Gang An, PhD&MD

Phone: 008613502181109
Email: angang@ihcams.ac.cn

Start date: April 20, 2023

Completion date: April 2027

Lead sponsor:
Agency: Institute of Hematology & Blood Diseases Hospital, China
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/NCT05850286