Bortezomib, Pomalidomide, Dexamethasone for Systemic AL Amyloidosis

Jin Lu, MD

Status and phase: Enrolling; Phase 2

Conditions: Systemic Amyloidosis

Treatments: Drug: Pomalidomide; Drug: Bortezomib; Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT06342466

2023-358-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

BPd

Experimental group

Description:

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.

Treatment:

Drug: Dexamethasone

Drug: Bortezomib

Drug: Pomalidomide