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

NCT05850286 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IIT2022063（2）
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• complete response rate (CRR)

  CRR(including sCR / CR , based on IMWG 2016 efficacy evaluation criteria)

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 12 months after the second CAR-T cell transfusion

• Overall response rate (ORR)

  ORR(including sCR / CR / VGPR / PR, based on IMWG 2016 efficacy evaluation criteria)

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 12 months after the second CAR-T cell transfusion

• Negative MRD rate

  Rate of negative minimal residual disease

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 12 months after the second CAR-T cell transfusion

• Overall Survival (OS)

  Occurrence of death regardless of cause

  1 year

• Progression free survival (PFS)

  Duration from start of study treatment to PD or death (regardless of cause), whichever comes first

  1 year

• Duration of Remission(DOR)

  Duration from the first evaluation of at least partial remission (PR) to the onset of disease progression or death due to disease progression (whichever occurs first)

  2 year

Secondary Outcomes (1)

• The incidence of treatment-emergent adverse events (TEAEs)

  2 year

Other Outcomes (1)

• The CART cell duration in vivo

  1 year

Study Arms (1)

VRD-based Regimen Combined With CART-ASCT-CART2

EXPERIMENTAL

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.

Biological: anti-BCMA CAR-T; Drug: VRD-based Regimen

Interventions

anti-BCMA CAR-T BIOLOGICAL

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.

VRD-based Regimen Combined With CART-ASCT-CART2

VRD-based Regimen DRUG

Bortezomib, Lenalidomide and Dexamethasone

VRD-based Regimen Combined With CART-ASCT-CART2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent (ICF) .
• Age ≥ 18 years and ≤ 65 years.
• 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)
• 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.
• 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
• 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.
• ECOG scores 0 - 1;
• No active infection
• 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).
• normal pulmonary function and oxygen saturation ≥ 92% on room air.
• 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%)
• Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.

You may not qualify if:

• Plasma cell leukemia.
• Documented active amyloidosis.
• Multiple myeloma with central nervous system (CNS) invasion
• Unsuitable for autologous stem cell transplantation, such as severe cardiopulmonary disorders
• 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
• Known intolerance, hypersensitivity, or contraindication to BCMA-CART cellular products.
• Patients with unstable or active cardiovascular system disease, meeting any of the following:
• Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarction or coronary artery reconstruction within 180 days prior to the first dose.
• Uncontrolled hypertension (\>140/90 mmHg with blood pressure fluctuations of more than 180/100 mmHg over a 6-month period).
• 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)).
• Congestive heart failure (CHF) classification ≥ grade 3 as defined by the New York Heart Association (NYHA).
• Left ventricular ejection fraction (LVEF) \<50% on echocardiography.
• History of stroke or intracranial haemorrhage within 12 months prior to screening.
• Presence of a serious thrombotic event prior to treatment.
• Known positive serology for HIV or HIV seropositivity.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

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

Tianjin, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Gang An, PhD&MD

CONTACT

86-022-23909171; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 9, 2023
• Study Start: April 21, 2023
• Primary Completion: October 1, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 4, 2025

Record last verified: 2025-06

Locations

CN (1)