Daratumumab for Patients With Light Chain Amyloidosis

Not Applicable

Recruiting

• Conditions: Light Chain (AL) Amyloidosis
• Interventions: Drug: Dratumumab / Hyaluronidase Injection [Darzalex Faspro]; Drug: Pomalidomide 4 MG; Procedure: autologous stem cell transplantation (ASCT)

• Registration Number: NCT06376214
• Lead Sponsor: Nanjing University School of Medicine

Brief Summary

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.

Study Timeline

• Study Start: 2023-01-01
• Study First Submitted: 2024-03-29
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Study First Posted: 2024-04-19
• Last Update Posted: 2024-04-19
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Participants must be aged ≥18 and ≤75 years;
2. Newly diagnosed AL amyloidosis ((confirmed by pathological examination with at least one major organ involvement (heart, kidney, or liver));
3. 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;
4. Participants must personally sign an informed consent form approved by the Ethics Committee before the start of the study;
5. Expected survival ≥ 12 weeks;
6. ECOG performance status≤ 2;
7. 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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Daratumumab and Dexamethasone combined with pomalidomide (DPD) (group C)	Pomalidomide 4 MG	newly diagnosed stage IIIb AL amyloidosis patients will received Daratumumab (16mg/kg), dexamethasone (40mg) and pomalidomide. The usage of Daratumumab and dexamethasone is the same as group A. 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.
daratumumab combine with ASCT treatment group (group B)	Dratumumab / Hyaluronidase Injection [Darzalex Faspro]	This group of patients will first receive two courses of treatment with the standard protocol of daratumumab combined with dexamethasone. Subsequent patients will receive ASCT treatment, and patients who achieve VGPR or CR after transplantation treatment will be followed up for observation
Daratumumab and Dexamethasone combined with pomalidomide (DPD) (group C)	Dratumumab / Hyaluronidase Injection [Darzalex Faspro]	newly diagnosed stage IIIb AL amyloidosis patients will received Daratumumab (16mg/kg), dexamethasone (40mg) and pomalidomide. The usage of Daratumumab and dexamethasone is the same as group A. 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.
long-term daratumumab treatment group (group A)	Dratumumab / Hyaluronidase Injection [Darzalex Faspro]	The patient will receive the standard protocol of daratumumab combined with dexamethasone treatment, once a week for the first two months, once every two weeks for four months, and then once a month for 18 months.
daratumumab combine with ASCT treatment group (group B)	autologous stem cell transplantation (ASCT)	This group of patients will first receive two courses of treatment with the standard protocol of daratumumab combined with dexamethasone. Subsequent patients will receive ASCT treatment, and patients who achieve VGPR or CR after transplantation treatment will be followed up for observation

Primary Outcome Measures

Name	Time	Method
Organ response rate	1 year	the 1-year organ response rate after treatment
Hematological complete response rate	6 months	the 6 months overall hematologic complete response rate after treatment.

Secondary Outcome Measures

Name	Time	Method
Time to Next Treatment	3 years	Number of months from study drug initiation to starting another treatment
Progression-free survival	3 years	the 3 years progression-free survival after treatment
Overall survival	5 years	the 5 years overall survival after treatment

Trial Locations

Locations (1)

National Clinical Research Center for Kidney Diseases, Jinling Hospital; 🇨🇳 Nanjing, Jiangsu, China