A Study of VRD-based Regimen Combined With CART-ASCT-CART2 Treatment in Patients With Primary Plasma Cell Leukemia

NCT05870917 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IIT2022064
• 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-based Regimen (Bortezomib, Lenalidomide and Dexamethasone) combined with CART-ASCT-CART2 in Chinese patients with newly diagnosed primary plasma cell leukemia.

Conditions

Plasma Cell Leukemia

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  The incidence of treatment-emergent adverse events (TEAEs)

  2 year

• Overall response rate (ORR)

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

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion

• Progression free survival (PFS)

  Is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first.

  1 year

Secondary Outcomes (4)

• Complete response rate (CRR)

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion

• Overall survival (OS)

  1 year

• MRD-negative Rate

  after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion

• Duration of Remission (DOR)

  2 year

Other Outcomes (1)

• The CART cell duration in vivo

  1 year

Study Arms (1)

VRD-based regimen Combined CART-ASCT-CART2

EXPERIMENTAL

VRD：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle. Autologous BCMA-directed CAR-T cells, Double infusion intravenously at a target dose of (2-4)±20％ x 10\^6 anti-BCMA CAR+T cells/kg respectively. Participants will receive VRD-based induction, first CAR-T infusion, VR consolidation, ASCT followed by the second CAR-T infusion, and R maintenance.

Biological: anti-BCMA CAR-T

Interventions

anti-BCMA CAR-T BIOLOGICAL

Autologous BCMA-directed CAR-T cells, the double infusion intravenously at a target dose of (2-4)±20％ x 10\^6 anti-BCMA CAR+T cells/kg respectively

Also known as: Bortezomib, Lenalidomide and Dexamethasone

VRD-based regimen Combined 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:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Age ≥ 18 years and ≤ 65 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Life expectancy at least 3 months
• Definitive diagnosis of pPCL: meet the diagnosis criteria of multiple myeloma (refer to the Chinese guidelines for the diagnosis and management of multiple myeloma (revised 2022) criteria) and meeting any of the following:
• the proportion of tumor plasma cells in peripheral blood leukocytes ≥ 5%;
• absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10\^9/L.
• Patients have not received previous anti-myeloma related therapy.
• Measurable disease, as defined by at lease one of the following:
• Serum monoclonal paraprotein (M-protein) level ≥5g/L.
• urine M-protein level ≥200 mg/24 hours.
• If the serum and urine M-protein are unmeasurable, abnormal serum free light chain (FLC) ratio and affected FLC ≥10 mg/dL.
• Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
• 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) : ANC ≥ 1.0 x 10\^9/L, PLT ≥ 50 x 10\^9/L.
• 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:

You may not qualify if:

• Secondary plasma cell leukemia.
• With central nervous system (CNS) involvement.
• Ineligible for autologous stem cell transplantation, such as severe cardiopulmonary disorders.
• Known intolerant, allergic, or resistant to glucocorticoids, bortezomib, lenalidomide, Venetoclax, Selinexor and BCMA-CART cellular products.
• Patients 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.
• 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.
• 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.

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

Leukemia, Plasma Cell

Interventions

Bortezomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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 29, 2023
• First Posted: May 23, 2023
• Study Start: April 25, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-01

Locations

CN (1)