Bortezomib, Pomalidomide, Dexamethasone for Systemic AL Amyloidosis

A Study of Bortezomib, Pomalidomide, Dexamethasone in Patients with Systemic AL Amyloidosis

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed or previous treated systemic light chain (AL) amyloidosis. Approximately 40 subjects will receive therapy with bortezomib, pomalidomide, and dexamethasone. The primary outcome is hematologic very good partial response and complete response rate at 6 months.

Study Overview

• Status: Recruiting
• Conditions: Systemic Amyloidosis
• Intervention / Treatment: Drug: Bortezomib; Drug: Pomalidomide; Drug: Dexamethasone

Detailed Description

Proteasome inhibitor and immunmodulators have synergistic effect for plasma cell dyscrasia. Due to the fact that more than 70-80% of patients with amyloidosis have renal involvement, the application of lenalidomide is limited. Thus, the investigators designed this open-label, multicenter, phase 2 study for newly diagnosed or previously treated systemic AL amyloidosis with bortezomib, pomalidomide and dexamethasone regimen.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Liu, Dr; Phone Number: 86-13716926210; Email: pkuphliuyang@vip.sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Yang Liu; Phone Number: +8613716926210; Email: pkuphliuyang@bjmu.edu.cn
      • Contact: Jin Lu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of AL amyloidosis, confirmed by histology and typed with immunohistochemistry, immunoelectron microscopy or mass spectrometry.
2. Newly diagnosed or previous treated AL amyloidosis
3. Patients must be ≥ 18 years of age.
4. ECOG performance status 0, 1 or 2.

5. Measurable disease defined by at least one of the following:

   ① serum free light chain (FLC) ≥2.0 mg/dL (20 mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) ≥2mg/dL (20 mg/L).

   ②. presence of a monoclonal spike that is ≥5 g/l.

6. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
7. Absolute neutrophil count (ANC) ≥1.0 X 10^9/L, Hemoglobin ≥70 g/L, Platelets ≥50 X 10^9/L
8. eGFR ≥20 mL/min/ 1.73 m^2
9. Written informed consent in accordance with local and institutional guidelines.
10. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

1. Fulfill with the criteria of active multiple myeloma or active lymphoplasmacytic lymphoma.
2. Presence of other tumors which is/are in advanced malignant stage and has/have systemic metastasis;
3. Severe or persistent infection that cannot be effectively controlled;
4. Presence of severe autoimmune diseases or immunodeficiency disease;
5. Patients with active hepatitis B or hepatitis C ([HBVDNA+] or [HCVRNA+]);
6. Patients with HIV infection or syphilis infection;
7. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

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: BPd; BPd regimen (Bortezomib, pomalidomide, and dexamethasone) will be applied every 28 days until progression of disease, unacceptable toxicity or subsequent therapy, for a maximum of six cycles.	Drug: Bortezomib; Bortezomib 1.3mg/m2 sc weekly; Other Names: Velcade; Drug: Pomalidomide; 4mg per day taken orally on 1-21 of repeated 28-day cycles; Drug: Dexamethasone; Dexamethasone 20mg-40mg weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic VGPR + CR rate at 6 months	Hematologic very good partial response plus complete response rate at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Hematologic response rate at 6 months	Overall Hematologic partial response, very good partial response rate and complete response at 6 months	6 months
At least one organ response at 6 months	At least one organ response (cardiac response, renal response, liver response) at 6 months	6 months
TTNT at 2 years	Time to next treatment at 2 years	2 years
Estimated PFS at 2 years	Estimated Progression free survival at 2 years	2 years
Estimated OS at 2 years	Estimated Overall Survival at 2 years	2 years
TRAE	Treatment-related adverse events up to 6 months	6 months

Collaborators and Investigators

• Sponsor: Jin Lu, MD
• Investigators: Principal Investigator: Jin Lu, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Paraproteinemias; Proteostasis Deficiencies; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bortezomib; Dexamethasone; Pomalidomide
• Other Study ID Numbers: 2023-358-02

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