An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis
Rajshekhar Chakraborty, MD
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.
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 t…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age ≥ 18 years at time of signing Informed Consent Form * Ability to comply with the study protocol, in the investigator's judgment * Confirmed diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) on a tissue biopsy * Has received ≥1 prior lines of therapy, including an anti-cluster of differentiation 38 (CD 38) monoclonal antibody * Participants with a history of autologous hematopoietic cell transplantation must have recovered from any transplant-related toxicities * Presence of t(11;14) on FISH at any time since diagnosis (Eligibilit…
Interventions
- DrugVenetoclax Oral Tablet, 200 mg
200 mg oral tablet daily
- DeviceFISH 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.
- DrugVenetoclax Oral Tablet, 400 mg
400 mg oral tablet daily
- DrugDexamethasone Oral, 10 mg
10 mg oral tablet weekly
- DrugDexamethasone Oral, 20 mg
20 mg oral tablet weekly
- DrugDaratumumab 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.
Locations (4)
- Boston Medical CenterBoston, Massachusetts
- Mayo Clinic RochesterRochester, Minnesota
- New York Presbyterian Hospital/Columbia University Irving Medical CenterNew York, New York
- Froedtert Hospital & the Medical College of WisconsinMilwaukee, Wisconsin