Daratumumab for Patients With Light Chain Amyloidosis

NCT ID: NCT06376214

Last Updated: 2024-04-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2026-12-31

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.

Conditions

Light Chain (AL) Amyloidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

long-term daratumumab treatment group (group A)

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.

Group Type: ACTIVE_COMPARATOR

Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Intervention Type: DRUG

Daratumumab will be administered at the FDA-approved dose of 16mg/kg as an intravenous infusion.

daratumumab combine with ASCT treatment group (group B)

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

Group Type: EXPERIMENTAL

Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Intervention Type: DRUG

Daratumumab will be administered at the FDA-approved dose of 16mg/kg as an intravenous infusion.

autologous stem cell transplantation (ASCT)

Intervention Type: PROCEDURE

The ASCT protocol included mobilisation with colony-stimulating factor alone and conditioning with high-dose melphalan140-200 mg/m2

.

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

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.

Group Type: EXPERIMENTAL

Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Intervention Type: DRUG

Daratumumab will be administered at the FDA-approved dose of 16mg/kg as an intravenous infusion.

Pomalidomide 4 MG

Intervention Type: DRUG

Patients received oral pomalidomide on days 1-21 of a 28-days cycle from cycle 1 to 6.

Interventions

Dratumumab / Hyaluronidase Injection [Darzalex Faspro]

Daratumumab will be administered at the FDA-approved dose of 16mg/kg as an intravenous infusion.

Intervention Type: DRUG

Pomalidomide 4 MG

Patients received oral pomalidomide on days 1-21 of a 28-days cycle from cycle 1 to 6.

Intervention Type: DRUG

autologous stem cell transplantation (ASCT)

The ASCT protocol included mobilisation with colony-stimulating factor alone and conditioning with high-dose melphalan140-200 mg/m2

.

Intervention Type: PROCEDURE

Other Intervention Names

DARA

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Zhi-Hong Liu, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xianghua Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Jinling Hospital, China

Locations

National Clinical Research Center for Kidney Diseases, Jinling Hospital

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xianghua Huang, MD

Role: CONTACT

hxhszb@163.com

02580862351

Facility Contacts

Xianghua Huang, MD

Role: primary

hxhszb@163.com

02580862351

Other Identifiers

2024-02

Identifier Type: -

Identifier Source: org_study_id