Clinical Study of Reduced-dose Pomalidomide and Cyclophosphamide Combined With Dexamethasone in the Treatment of Patients With Debilitating RRMM

A Multicenter, Open-label Clinical Study of a Reduced-dose Pomalidomide and Cyclophosphamide Combined With Dexamethasone Regimen for the Treatment of Patients With Debilitating Relapsed-refractory Multiple Myeloma

This is an open-label clinical study to evaluate the efficacy and safety of a multicenter, open-label clinical study of a base-reduced-dose pomalidomide, cyclophosphamide combined with dexamethasone (PCd) regimen for the treatment of patients with debilitating relapsed refractory multiple myeloma.

Subjects meeting the enrollment criteria were screened for entry into the study and treated with the appropriate regimen; all patients enrolled in the study did not receive medications other than those specified in the regimen for the treatment of myeloma during the study period, except for supportive care. The primary endpoint of the study is ORR; secondary study endpoints include efficacy above VGPR, progression-free survival (PFS), overall survival (OS), TTNT, safety, and life scale assessment.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma in Relapse
• Intervention / Treatment: Drug: Pomalidomide, cyclophosphamide combined with dexametha

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weiwei Tian, Doctor; Phone Number: +8613485304136; Email: 408933582@qq.com
• Study Contact Backup: Name: Jie Zhao, Master; Phone Number: +8618734895885; Email: 429809209@qq.com

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030032
      • Recruiting
      • ShanxiBethuneH
      • Contact: Weiwei Tian; Phone Number: +8613485304136; Email: tianweiwei@yeah.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Patients with relapsed/refractory MM, including extramedullary infiltration (meeting IMWG 2016 diagnostic criteria);
• IMWG frailty assessment: frail patients.
• Patients with multiple myeloma who have relapsed after previous treatment with 1-3 regimens;
• Patients unresponsive or unable to undergo autologous stem cell transplantation and with disease progression or resistance after prior treatment with proteasome-containing inhibitors (bortezomib) or immunomodulators (thalidomide, lenalidomide); tolerant to more than one of the above drugs;
• Serum monoclonal protein (M protein) reaches measurable levels: serum M protein ≥ 5 g/L; or 24h urinary light chain > 200mg; or serum free light chain > 10mg/dL;
• The patient's clinical indicators must meet the following criteria:ANC ≥ 1.0 x 109/L and PLT ≥ 75 x 109/L for myeloma cells < 50%; any ANC and PLT ≥ 50 x 109 for myeloma cells ≥ 50%; platelets or granulocyte colony-stimulating factor (G-CSF) may be infused to help patients meet the eligibility criteria, but are not permitted within the first 3 days of enrollment; Patients with a glomerular filtration rate ≥10 mL/min who do not require dialysis;
• Patients who have not undergone major surgery, radiation therapy, or participated in another research trial within 2 weeks and have recovered from clinical toxicity of prior therapy;
• with follow-up conditions. Patients understand the characteristics of the disease they suffer from and voluntarily enroll in this study protocol for treatment and follow-up;
• Informed consent has been signed. Informed consent was signed by the patient himself/herself or his/her immediate family members. From the patient's condition, if the patient's own signature is not conducive to the treatment of the condition, then the legal guardian or the patient's immediate family members will sign the informed consent.

Exclusion Criteria:

• Patients with newly diagnosed multiple myeloma (NDMM), plasma cell leukemia;
• Previous use of pomalidomide, cyclophosphamide;
• patients with cyclophosphamide, dexamethasone allergy/intolerance;
• patients with active hepatitis B (HBV), hepatitis C (HCV), and other acquired and congenital immunodeficiency diseases;
• hepatic insufficiency (bilirubin > 3.1mg/100m, ALT and AST > 2 times the upper limit of normal value);
• The presence of severe thrombotic events before treatment;
• Patients with comorbid uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) defined class III-IV heart failure, uncontrolled angina, clinically significant pericardial disease or cardiac amyloidosis;
• Infection requiring systemic antibiotic therapy, or other serious infection within 14 days;
• Those who underwent major surgery within 30 days prior to enrollment;
• those who require medication for epilepsy, dementia and other abnormal mental conditions who are unable to understand or comply with the study protocol;
• Patients with serious physical or mental illnesses that, in the judgment of the protocol or the investigator, are likely to interfere with participation in this clinical study;
• Substance abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the study or the evaluation of study results;
• persons who, in the opinion of the investigator, are not suitable for enrollment.

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: Reduced-dose pomalidomide/cyclophosphamide/dexamethasone (PCd) regimen group

Drug: Pomalidomide, cyclophosphamide combined with dexametha; The starting dose of pomalidomide was 2 mg in all cases，the starting dose of cyclophosphamide was 50 mg/day.If the adverse event is attributable to a specific study drug, the dose is reduced accordingly for that drug; if the adverse event is associated with multiple drugs, the dose is reduced appropriately for one of the predominantly associated drugs at the discretion of the investigator; and if multiple adverse events occur concurrently, the dose should be adjusted according to the guidelines for the most severe toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	up to 2 years
Efficacy above VGPR	Stringent complete response is defined as fulfilling the criteria for CR combined with a normal serum free light chain ratio and the absence of clonal plasma cells in the bone marrow as confirmed by immunohistochemistry. CR is negative serum and urine immunofixation electrophoresis, disappearance of soft tissue plasmacytomas, and <5% plasma cells in the bone marrow. Very good partial response (VPR) is a serum protein electrophoresis with no detectable M protein, but serum and urine immunofixation electrophoresis are still positive; or a reduction in M protein of ≥90% and urinary M protein <100mg/24h.	up 3 years
PFS	progression-free survival (within 2 years)	within 2 years
duration from start of study treatment with all 3 agents to start of any new line of treatment		up to 3 years
safety of drugs	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and EORTC QLQ-C30.	up to 2 years
life scale assessment above VGPR（very good partial response）	EORTC QLQ-C30 (1-3 months/dose)	up to 3 years

Collaborators and Investigators

• Sponsor: Shanxi Bethune Hospital
• Investigators: Principal Investigator: Xiaomin Zhang, Shanxi Bethune Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): June 15, 2025

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: February 4, 2024
• First Posted (Estimated): February 13, 2024

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Cyclophosphamide; Pomalidomide
• Other Study ID Numbers: YXLL-2022-073

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No