A Phase Ib/II Clinical Study on the Application of Linperlisib Combined with the VRD Regimen in Newly Diagnosed Patients with Multiple Myeloma

A Single-Arm, Multicenter, Open-Label Phase Ib/II Clinical Study on the Application of Linperlisib Plus the VRD Regimen in Newly Diagnosed Patients with Multiple Myeloma

This study aims to evaluate the safety and efficacy of Linperlisib combined with the VRD regimen in the treatment of newly diagnosed patients with multiple myeloma. The study is divided into a Phase Ib dose exploration phase and a Phase II expansion phase.The Phase Ib dose exploration phase primarily aims to determine the recommended Phase II dose (RP2D) of Linperlisib based on dose-limiting toxicity (DLT). The Phase II expansion phase involves induction therapy using at least four cycles of Linperlisib at RP2D in combination with the VRD regimen. After completing four cycles of induction therapy, patients eligible for autologous hematopoietic stem cell transplantation (ASCT) will undergo the procedure. For patients whose therapeutic evaluation results in PD (progressive disease) or SD (stable disease), alternative treatment regimens will be considered based on their condition. After successful transplantation, 2-4 cycles of the original induction regimen will be used for consolidation therapy.The primary objective is to evaluate the proportion of patients achieving a very good partial response (VGPR) after four cycles of induction therapy with the Linperlisib combined VRD regimen.

Study Overview

• Status: Not yet recruiting
• Conditions: Newly Diagnosed Multiple Myeloma
• Intervention / Treatment: Drug: a combination treatment of Linperlisib and the VRD regimen

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Fuling Zhou, Doctor; Phone Number: 027-67813137; Email: zhoufuling@whu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • the First Affiliated Hospital of Zhengzhou University
      • Contact: Chong Wang
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
      • Contact: Fuling Zhou, director; Phone Number: +86-02767813137; Email: zhoufuling@whu.edu.cn
    • Xianning, Hubei, China, 437100
      • Xianning Central Hospital
      • Contact: RenYing Ge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Patients must be newly diagnosed with active multiple myeloma. 2. Patients must be between 18 and 65 years old and eligible for autologous hematopoietic stem cell transplantation (ASCT).

  3. Patients must have measurable disease, defined as follows:

• Any quantifiable serum monoclonal protein level (typically but not necessarily ≥0.5 g/dL of M-protein), and/or urinary light chain excretion >200 mg/24 hours.

• For oligosecretory or non-secretory multiple myeloma (MM), patients must have measurable plasmacytomas >2 cm confirmed by clinical examination or imaging (e.g., MRI, CT scan) or an abnormal free light chain (FLC) ratio (normal value: 0.26-1.65) with an involved FLC level ≥10 mg/dL.

  4. Patients must have an expected survival of ≥3 months. 5. Karnofsky Performance Status (KPS) score must be ≥60%. 6. Liver Function:

• Serum alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) ≤3 times ULN.

• Direct bilirubin ≤2 mg/dL (34 µmol/L) within 14 days prior to randomization. 7. Neutrophil and Platelet Counts: Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L within 14 days prior to randomization.Platelet count ≥75 × 10⁹/L (or ≥50 × 10⁹/L if >50% of bone marrow is involved with myeloma) within 14 days prior to randomization.

  8. Creatinine clearance (CrCl) ≥30 mL/min, measured or calculated using standard formulas (e.g., Cockcroft-Gault) within 7 days prior to randomization.

  9. Corrected serum calcium levels must be ≤14 mg/dL (3.5 mmol/L). 10. Left ventricular ejection fraction (LVEF) must be ≥40%. Two-dimensional transthoracic echocardiography (ECHO) is the preferred method for assessment. If ECHO is unavailable, a multigated acquisition scan (MUGA) is acceptable.

  11. Patients must be able to understand and voluntarily sign the informed consent form.

  12. Women with childbearing potential must agree to undergo pregnancy testing and use contraception.

  13. Male subjects must agree to use contraception.

Exclusion Criteria:

• 1. Patients who have previously received anti-myeloma therapy, except for radiotherapy, bisphosphonates, or a single short course of steroids (≤40 mg/day of dexamethasone equivalent for up to 4 days).

  2. Non-secretory MM patients, unless they have abnormal serum free light chains or a measurable plasmacytoma with a minimum maximum diameter >2 cm.

  3. Patients who do not meet the eligibility criteria for autologous stem cell transplantation.

  4. Women who are pregnant or breastfeeding. 5. Acute active infections requiring treatment (ongoing use of systemic antibiotics, antiviral, or antifungal agents) within 14 days prior to randomization.

  6. Patients with known human immunodeficiency virus (HIV) infection. 7. Active hepatitis A, B, or C infection. 8. Patients with the following cardiac conditions within 4 months prior to randomization:

• Unstable angina or myocardial infarction.
• New York Heart Association (NYHA) Class III or IV heart failure.
• Uncontrolled angina.
• Severe coronary artery disease.
• Severe ventricular arrhythmias.
• Sick sinus syndrome.
• Acute ischemia.

• Electrocardiographic evidence of Grade 3 conduction abnormalities, unless the patient has a pacemaker.

  9. Severe neuropathy (Grade 3-4 or Grade 2 with pain) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC) Version 4.0 within 14 days prior to randomization.

  10. Known allergy to any of the investigational drugs. 11. Patients with contraindications to required concomitant medications or supportive therapies, including hypersensitivity to all anticoagulants, antiplatelets, or antiviral agents, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment.

  12. Any other clinically significant disease or condition that, in the investigator's opinion, could interfere with protocol adherence or the patient's ability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: enrollment cohort; Phase Ib ：Subjects will be administered Linperlisib orally at doses of 40 mg, 60 mg, or 80 mg once daily for 4 consecutive weeks, combined with the standard-dose VRD regimen. The dose-limiting toxicity (DLT) observation period is set at 28 days. If no DLT or other serious adverse events (SAEs) related to the investigational drug occur during the DLT observation period, the subject will proceed to subsequent treatment. In the absence of serious adverse events related to the investigational drug, the dose will be escalated to the next cohort based on the dose escalation principle. The Phase II expansion phase involves induction therapy with at least four cycles of Linperlisib at the recommended Phase II dose (RP2D) in combination with the VRD regimen. After completing four cycles of induction therapy, patients who meet the criteria for autologous hematopoietic stem cell transplantation (ASCT) will undergo the procedure. If a patient's therapeutic evaluation results in progressive disea

Drug: a combination treatment of Linperlisib and the VRD regimen; Subjects will be administered Linperlisib orally at doses of 40 mg, 60 mg, or 80 mg once daily for 4 consecutive weeks, combined with the VRD regimen at standard doses. Subsequently, during the expansion phase, at least four cycles of Linperlisib at the recommended Phase II dose (RP2D) will be combined with the VRD regimen for induction therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity (DLT)	The primary objective is to determine the recommended Phase II dose (RP2D) of Linperlisib based on dose-limiting toxicity (DLT).	At the end of Cycle 4 (each cycle is 28 days)
VGPR Rate	The very good partial response (VGPR) rate is evaluated based on the 2016 International Myeloma Working Group (IMWG) criteria.	At the end of Cycle 4 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from the patient's first dose of medication to the time of death from any cause.	Time from the patient's first dose of medication to death from any cause (Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any cause, whichever comes first)
Complete remission rate	Bone marrow primitive cells <5%, no primitive cells with Auer vesicles, no primitive cells in the peripheral blood, no extramedullary leukaemia, neutrophil count ≥1.0×109/L, platelet count ≥100×109/L	At the end of Cycle 4 (each cycle is 28 days)
Progression-Free Survival (PFS)	The length of time during and after treatment that a patient lives without any signs of disease progression, assessed after completing induction therapy, ASCT, and consolidation therapy.	Time from the patient's first dose of medication to death from any cause (Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any cause, whichever comes first)
Incidence of adverse events	Incidence of adverse events, e.g., GI adverse reactions, cardiotoxicity, etc.	At the end of Cycle 4 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Fuling Zhou
• Investigators: Study Director: Fuling Zhou, Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: multiple myeloma; PI3Kδ inhibitor; Linperlisib
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No