NCT05451771

Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis

An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: Rajshekhar Chakraborty, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is assess safety, safest dose, and effectiveness of venetoclax in combination with dexamethasone in participants with t(11;14) positive relapsed (comes back) or refractory (did not get better) light chain amyloidosis.

Detailed description

This study is a phase 1/2 study of venetoclax-dexamethasone combination therapy in relapsed/refractory t(11;14) systemic immunoglobulin light chain amyloidosis (AL) amyloidosis. The phase 1 is a dose escalation designed to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of venetoclax in combination with low-dose weekly dexamethasone. There will be four candidate-dosing cohorts of venetoclax with or without dexamethasone in the Phase I dose-escalation. Dose escalation will be guided by the Bayesian optimal interval (BOIN) design with accelerated titration up to a total sample size of 15 participants. The phase 2 portion is a randomized open-label study comparing the MTD or RP2D of venetoclax in combination with dexamethasone versus investigator's choice (daratumumab, pomalidomide, bendamustine, or ixazomib (with or without dexamethasone).

Conditions

• AL Amyloidosis

Interventions

Type	Name	Description
DRUG	Venetoclax Oral Tablet, 200 mg	200 mg oral tablet daily
DEVICE	FISH assay	Cytogenetic analysis is intended for evaluation of relapsed/refractory AL amyloidosis using fluorescence in situ hybridization (FISH) using known translocation probes. Bone marrow aspirate (BMA) samples are collected in lavender top (Ethylenediaminetetraacetic acid (EDTA)) or green top (Sodium heparin) tubes. Specimen tubes shall be transported at room temperature to the laboratory on the same day of collection.
DRUG	Venetoclax Oral Tablet, 400 mg	400 mg oral tablet daily
DRUG	Dexamethasone Oral, 10 mg	10 mg oral tablet weekly
DRUG	Dexamethasone Oral, 20 mg	20 mg oral tablet weekly
DRUG	Daratumumab Injection	Daratumumab will be administered at a dose of 16 mg/kg by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter for a maximum of 6 months of therapy. If subcutaneous formulation is available, participants can also receive subcutaneous daratumumab (1800 mg in 15 ml) in the same schedule.
DRUG	Bendamustine	Bendamustine will be given at an initial dose of 100 mg/m\^2 intravenously on days 1 and 2 in each 28-day cycle.
DRUG	Pomalidomide	Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.
DRUG	Ixazomib	Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.
DRUG	Venetoclax MTD with Dexamethasone	Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results

Timeline

• Start date: 2022-10-26
• Primary completion: 2026-09-01
• Completion: 2026-09-01
• First posted: 2022-07-11
• Last updated: 2025-07-08

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study