Optimize First-line Treatment for AL Amyloidosis With t (11; 14)

Not Applicable

Recruiting

• Conditions: AL Amyloidosis; Amyloidosis; Systemic
• Interventions: Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone; Drug: Venetoclax

• Registration Number: NCT06192979
• Lead Sponsor: Jin Lu, MD

Brief Summary

Achievement of complete hematologic response (CHR) is vital for systemic AL amyloidosis. Currently, the CHR rate of daratumumab, bortezomib, and dexamethasone (DBD) is close to 60%. Considering that Bcl-2 inhibitor is effective for AL amyloidosis with t(11; 14) and the median hematologic onset time of DBD is 7 days. We design a a prospective study on AL amyloidosis with t(11; 14). All patients receive DBD at the beginning. Patient will receive DBD for at least 6 cycles if achieve rapid hematologic response at day 7, while other patients will receive daratumumab, venetoclax and dexamethasone.

Detailed Description

The goal of this clinical trial is to optimize the first line treatment for systemic AL amyloidosis with t(11;14). The aim of this study is to pursue early complete hematologic response. The primary endpoint is overall complete hematologic response (CHR) rate at 6 months. Participants will be treated according to the hematologic response after 7 days. If the patient get rapid response after 7 days, he/she will receive daratumumab, venetoclax and dexamethasone (DBD) for at least 6 cycles. If the patient do not get rapid response, he/she will receive daratumumab, venetoclax and dexamethasone.

Study Timeline

• Study First Submitted: 2023-12-12
• Study First Submitted QC: 2023-12-21
• Study Start: 2024-01-05
• Study First Posted: 2024-01-05
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-03
• Last Update Posted: 2024-02-06
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1. Diagnosis of systemic AL amyloidosis;
2. Daratumumab, bortezomib, dexamethasone used in 1st line treatment;
3. Life expectancy greater than 12 weeks;
4. HGB ≥70g/L;
5. Blood oxygen saturation >90%;
6. Total bilirubin (TBil) ≤3×upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN;
7. Informed consent explained to, understood by and signed by the patient.

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rapid Response Group	Bortezomib	Daratumumab, bortezomib, dexamethasone
Rapid Response Group	Dexamethasone	Daratumumab, bortezomib, dexamethasone
Rapid Response Group	Daratumumab	Daratumumab, bortezomib, dexamethasone
Non-Rapid Response Group	Daratumumab	Daratumumab, venetoclax, dexamethasone
Non-Rapid Response Group	Venetoclax	Daratumumab, venetoclax, dexamethasone
Non-Rapid Response Group	Dexamethasone	Daratumumab, venetoclax, dexamethasone

Primary Outcome Measures

Name	Time	Method
Overall CHR rate at 6 months	Overall CHR rate at 6 months	Overall complete hematologic response rate at 6 months

Secondary Outcome Measures

Name	Time	Method
MRD status at 6 months	MRD status at 6 months	Minimal residual disease status at 6 months
TRAEs	TRAEs	treatment-related adverse events up to 6 months
Hepatic response at 6 months	Hepatic response at 6 months	Hepatic response at 6 months
Estimated 2-year OS	Estimated 2-year overall survival	Estimated 2-year overall survival
Cardiac response at 6 months	Cardiac response at 6 months	Cardiac response at 6 months
Renal response at 6 months	Renal response at 6 months	Renal response at 6 months
Estimated 2-year PFS	Estimated 2-year PFS	Estimated 2-year progression free survival

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China