Daratumumab for Patients With Light Chain Amyloidosis

Nanjing University School of Medicine

Status: Enrolling

Conditions: Light Chain (AL) Amyloidosis

Treatments: Drug: Dratumumab / Hyaluronidase Injection [Darzalex Faspro]; Drug: Pomalidomide 4 MG; Procedure: autologous stem cell transplantation (ASCT)

Study type: Interventional

Funder types: Other

Identifiers

NCT06376214

2024-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 3 patient groups

long-term daratumumab treatment group (group A)

Active Comparator group

Description:

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.

Treatment:

Drug: Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

daratumumab combine with ASCT treatment group (group B)

Experimental group

Description:

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

Treatment:

Procedure: autologous stem cell transplantation (ASCT)

Drug: Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Daratumumab and Dexamethasone combined with pomalidomide (DPD) (group C)

Experimental group

Description:

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.

Treatment:

Drug: Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Drug: Pomalidomide 4 MG