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

NCT ID: NCT05451771

Last Updated: 2025-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-26

Study Completion Date

2026-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

AL Amyloidosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase 1: Venetoclax 200 mg

Cohort 1: Venetoclax 200 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Group Type EXPERIMENTAL

Venetoclax Oral Tablet, 200 mg

Intervention Type DRUG

200 mg oral tablet daily

FISH assay

Intervention Type DEVICE

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.

Phase 1: Venetoclax 400mg

Cohort 2: Venetoclax 400 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Group Type EXPERIMENTAL

FISH assay

Intervention Type DEVICE

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.

Venetoclax Oral Tablet, 400 mg

Intervention Type DRUG

400 mg oral tablet daily

Phase 1: Venetoclax 400mg + Dexamethasone 10 mg

Cohort 3: Venetoclax 400 mg tablet, once daily and Dexamethasone 10 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Group Type EXPERIMENTAL

FISH assay

Intervention Type DEVICE

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.

Venetoclax Oral Tablet, 400 mg

Intervention Type DRUG

400 mg oral tablet daily

Dexamethasone Oral, 10 mg

Intervention Type DRUG

10 mg oral tablet weekly

Phase 1: Venetoclax 400mg + Dexamethasone 20 mg

Cohort 4: Venetoclax 400 mg tablet, once daily and Dexamethasone 20 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Group Type EXPERIMENTAL

FISH assay

Intervention Type DEVICE

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.

Venetoclax Oral Tablet, 400 mg

Intervention Type DRUG

400 mg oral tablet daily

Dexamethasone Oral, 20 mg

Intervention Type DRUG

20 mg oral tablet weekly

Phase 2: 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

Group Type EXPERIMENTAL

Venetoclax MTD with Dexamethasone

Intervention Type DRUG

Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results

Phase 2: Control Arm (Investigator's Choice)

Participants will receive one of the following as determined by the investigator:

Daratumumab, Pomalidomide, Bendamustine, or Ixazomib (+/- dexamethasone)

Group Type ACTIVE_COMPARATOR

Dexamethasone Oral, 20 mg

Intervention Type DRUG

20 mg oral tablet weekly

Daratumumab Injection

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.

Ixazomib

Intervention Type DRUG

Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Venetoclax Oral Tablet, 200 mg

200 mg oral tablet daily

Intervention Type DRUG

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.

Intervention Type DEVICE

Venetoclax Oral Tablet, 400 mg

400 mg oral tablet daily

Intervention Type DRUG

Dexamethasone Oral, 10 mg

10 mg oral tablet weekly

Intervention Type DRUG

Dexamethasone Oral, 20 mg

20 mg oral tablet weekly

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Pomalidomide

Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.

Intervention Type DRUG

Ixazomib

Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Venclexta t(11;14) FISH assay Venclexta Decadron Hemady Decadron Hemady Darzalex Treanda Pomalyst Ninlaro

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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%
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Rajshekhar Chakraborty, MD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Rajshekhar Chakraborty, MD

Assistant Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Rajshekhar Chakraborty, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Boston Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

New York Presbyterian Hospital/Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Research Nurse Navigator

Role: CONTACT

212-342-5162

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Boston Medical Center

Role: primary

617-638-8265

Mayo Clinic Rochester

Role: primary

8557760015

Research Nurse Navigator

Role: primary

212-342-5162

Froedtert Hospital & the Medical College of Wisconsin

Role: primary

414-805-8900

References

Explore related publications, articles, or registry entries linked to this study.

Locke M, Nieto M. AL Amyloidosis: Current Treatment and Outcomes. Adv Hematol. 2025 Mar 3;2025:7280805. doi: 10.1155/ah/7280805. eCollection 2025.

Reference Type DERIVED
PMID: 40226119 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

AAAT8639

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Teclistamab-Daratumumab in AL Amyloidosis
NCT07110844 RECRUITING PHASE2