Venetoclax-Dexamethasone in Relapsed and/​or Refractory t(11;14) Amyloidosis VENETOCLAX FOR T(11;14) AMYLOIDOSIS

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.

What will happen during the trial?

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).

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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 (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 Criteria:

* 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%

Additional Trial Information

Phase 1/2

Enrollment: 53 patients (estimated)

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Published Results

An open-label multicenter Phase 1/2 trial of venetoclax-dexamethasone in Relapsed/Refractory t(11;14)-positive systemic AL amyloidosis

November 03, 2025

Of 16 patients screened, 12 were enrolled and evaluable for safety and efficacy. Screen failures were attributed to second malignancy (n=2), t(11;14) positivity in <5% CD-138-selected cells (n=1), and t(11;14) negativity (n=1). Enrolled patients had a median age of 64 years, with 25% female, and 17% Black representation. At screening, the median percentage of CD-138-selected cells with t(11;14)-positivity on FISH was 65%. All patients had prior anti-CD38 mAb-exposure by protocol design, with 11/12 patients also exposed to bortezomib. The median number of prior lines of therapy was 1 (range, 1-5). Disease markers at treatment initiation included median dFLC of 14.35 mg/dL (range, 2.13-186.28), median NT-proBNP of 712.5 pg/mL (range, 54-8831), and the median serum creatinine of 0.99 mg/dL (range, 0.69-3.01).

Regarding safety, there were no DLTs encountered during the specified timeframe. One patient each received DLs 1, 2, and 3, with all remaining patients receiving DL 4 (400mg + dexamethasone 20mg weekly), which is the RP2D in this trial. There was only one patient that developed grade 3 infection (lung infection; COVID-19). No tumor-lysis syndrome, grade 3 or higher cytopenia, or treatment-emergent deaths occurred.

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Trial Locations

All Trial Locations

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Massachusetts

Boston Medical Center

Boston, MA

Open and Accepting

Minnesota

Mayo Clinic (Rochester)

Rochester, MN

Open and Accepting

New York

Herbert Irving Comprehensive Cancer Center (Columbia University) Columbia University Medical Center

New York, NY

Open and Accepting

Wisconsin

Medical College of Wisconsin Froedtert Hospital

Milwaukee, WI

Open and Accepting
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