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

N/ARecruitingNCT06192979

Jin Lu, MD41 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Amyloidosis; Systemic AL Amyloidosis

Interventions

DaratumumabDRUG

Daratumumab 16 mg/kg was administered intravenously weekly in cycles one and two, every two weeks for cycles three to six, for at least 6 cycles. Daratumumab and hyaluronidase-fihj 1800mg is allowed according to the patients' choice.

BortezomibDRUG

All patients received 1.0-1.3 mg/m2 subcutaneous bortezomib once weekly of 28 days each for at 6 cycles.

DexamethasoneDRUG

All patients received 20-40 mg oral or intravenous dexamethasone

VenetoclaxDRUG

All patients received venetoclax 400mg daily.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Overall CHR rate at 6 months

Overall complete hematologic response rate at 6 months

Time frame: Overall CHR rate at 6 months

Secondary Outcomes

Cardiac response at 6 months

Time frame: Cardiac response at 6 months

Renal response at 6 months

Time frame: Renal response at 6 months

Hepatic response at 6 months

Time frame: Hepatic response at 6 months

Estimated 2-year PFS

Estimated 2-year progression free survival

Time frame: Estimated 2-year PFS

Estimated 2-year OS

Estimated 2-year overall survival

Time frame: Estimated 2-year overall survival

MRD status at 6 months

Minimal residual disease status at 6 months

Time frame: MRD status at 6 months

TRAEs

treatment-related adverse events up to 6 months

Time frame: TRAEs