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

Phase 1

Not yet recruiting

• Conditions: Newly Diagnosed Multiple Myeloma
• Interventions: Drug: a combination treatment of Linperlisib and the VRD regimen

• Registration Number: NCT06799676
• Lead Sponsor: Fuling Zhou

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-16
• Study First Submitted QC: 2025-01-27
• Last Update Submitted: 2025-01-27
• Study First Posted: 2025-01-29
• Last Update Posted: 2025-01-29
• Study Start: 2025-02
• Primary Completion: 2027-08
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 42

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.

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

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

  12. 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.

  5. 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.

  11. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
enrollment cohort	a combination treatment of Linperlisib and the VRD regimen	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Complete remission rate	At the end of Cycle 4 (each cycle is 28 days)	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
Overall survival	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)	The time from the patient's first dose of medication to the time of death from any cause.
Incidence of adverse events	At the end of Cycle 4 (each cycle is 28 days)	Incidence of adverse events, e.g., GI adverse reactions, cardiotoxicity, etc.
Progression-Free Survival (PFS)	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)	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.

Trial Locations

Locations (3)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Zhongnan Hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China

Xianning Central Hospital; 🇨🇳 Xianning, Hubei, China