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
Rajshekhar Chakraborty, MD
53 participants
Oct 26, 2022
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria7
- 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 (Eligibility must confirmed by FISH testing at Columbia University Irving Medical Center (CUIMC)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Exclusion Criteria10
- Known hypersensitivity to any of the study drugs
- History of other malignancy that could affect compliance with the protocol or interpretation of results (Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.)
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal)
- Patients on renal replacement therapy
- Known GI disease or GI procedure that could interfere with oral absorption (including difficulty swallowing)
- New York Heart Association (NYHA) Class III or IV heart failure
- Mayo stage three-B (IIIB) with N-terminal pro-hormone B-type natriuretic peptide (NT-Pro BNP) > 8500 pg/mL
- Prior exposure to anti-apoptotic protein B-cell lymphoma 2 (BCL-2) inhibitors
- Patients with human immunodeficiency virus (HIV) who are not on highly active antiretroviral therapy (HAART) or those with active hepatitis A, B, or C infection
- Patients meeting criteria for symptomatic multiple myeloma by one of the following:(a) Lytic lesions on imaging (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, or (c) Bone marrow plasma cell infiltrate of greater than 60%
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Interventions
200 mg oral tablet daily
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.
400 mg oral tablet daily
10 mg oral tablet weekly
20 mg oral tablet weekly
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.
Bendamustine will be given at an initial dose of 100 mg/m\^2 intravenously on days 1 and 2 in each 28-day cycle.
Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.
Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.
Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results
Locations(4)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05451771