Daratumumab for Patients With Light Chain Amyloidosis

Official title

Daratumumab and Dexamethasone Combined With Pomalidomide (DPD) or ASCT in the Treatment of Newly Diagnosed Systemic Light Chain Amyloidosis (AL Amyloidosis): a Prospective, Single Center Clinical Trial

Overview

This is a prospective, single-center study exploratory clinical trial, aim to exploring the efficacy and safety of daratumumab in patients with AL amyloidosis, patients were divided into three groups: one group received long-term treatment with daratumumab based regimen, and the other group received autologous stem cell transplantation after two standard treatment courses with daratumumab based regimen, and the third group consists of newly diagnosed stage IIIb AL amyloidosis patients who plan to receive DPD treatment. The purpose of this study is to observe the efficacy and safety of Daratumumab, in the treatment of newly diagnosed systemic AL amyloidosis.

Detailed description

This is a prospective, single-center study exploratory clinical trial, aim to exploring the efficacy and safety of daratumumab in patients with AL amyloidosis, patients were divided into three groups: one group received long-term treatment with daratumumab based regimen (group A) and the other group received autologous stem cell transplantation after two standard treatment courses with daratumumab based regimen (group B) , and the third group consists of newly diagnosed stage IIIb AL amyloidosis patients who plan to receive DPD treatment (group C). Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression. Group C were given Daratumumab (16mg/kg), dexamethasone (40mg) and pomalidomide. The usage of Daratumumab and dexamethasone is the same as group A and B. Patients received oral pomalidomide on days 1-21 of a 28-days cycle from cycle 1 to 6. The dose of pomalidomide is adjusted based on the patient's renal function and ECOG score.

Interventions

• Drug Dratumumab / Hyaluronidase Injection [Darzalex Faspro]
  Daratumumab will be administered at the FDA-approved dose of 16mg/kg as an intravenous infusion.
• Drug Pomalidomide 4 MG
  Patients received oral pomalidomide on days 1-21 of a 28-days cycle from cycle 1 to 6.
• Procedure autologous stem cell transplantation (ASCT)
  The ASCT protocol included mobilisation with colony-stimulating factor alone and conditioning with high-dose melphalan140-200 mg/m2 .

Primary outcome measures

• Hematological complete response rate [Time frame: 6 months]
• Organ response rate [Time frame: 1 year]

Secondary outcome measures (3)

• Time to Next Treatment [Time frame: 3 years]
• Progression-free survival [Time frame: 3 years]
• Overall survival [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Participants must be aged ≥18 and ≤75 years;
• Newly diagnosed AL amyloidosis ((confirmed by pathological examination with at least one major organ involvement (heart, kidney, or liver));
• In group A and B, according to the Mayo 2004 staging system, the disease is classified as stage Ⅰ-ⅢA; In group C, according to the Mayo 2004 staging system, the disease is classified as stage IIIB: NT⁃proBNP>8500ng/L and cTnT>0.035μg/L or cTnI>0.01g/L;
• Participants must personally sign an informed consent form approved by the Ethics Committee before the start of the study;
• Expected survival ≥ 12 weeks;
• ECOG performance status≤ 2;
• Female participants of childbearing potential must agree to use effective contraception from the day of signing the informed consent until 365 days after the infusion. Effective contraception is defined as abstinence or the use of a contraceptive method with a failure rate of <1% per year.

Exclusion criteria

• eGFR< 30ml/min/1.73m2;
• Combined multiple myeloma;
• Acute or chronic infection requiring treatment within 30 days prior to baseline;
• Pregnant or breastfeeding women.
• Participants known to have life-threatening allergic reactions, hypersensitivity, or intolerance to Monoclonal antibodies or immune modulators.
• Other conditions deemed by the researcher as unsuitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• National Clinical Research Center for Kidney Diseases, Jinling Hospital — Nanjing

Identifiers

NCT: NCT06376214 · 2024-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗