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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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 (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%

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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)
  • Drug: Venetoclax Oral Tablet, 200 mg
    200 mg oral tablet daily
    Other names:
    • Venclexta
  • 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.
    Other names:
    • t(11;14) FISH assay
Experimental
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)
  • 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.
    Other names:
    • t(11;14) FISH assay
  • Drug: Venetoclax Oral Tablet, 400 mg
    400 mg oral tablet daily
    Other names:
    • Venclexta
  • Drug: Dexamethasone Oral, 10 mg
    10 mg oral tablet weekly
    Other names:
    • Decadron
    • Hemady
Experimental
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)
  • 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.
    Other names:
    • t(11;14) FISH assay
  • Drug: Venetoclax Oral Tablet, 400 mg
    400 mg oral tablet daily
    Other names:
    • Venclexta
  • Drug: Dexamethasone Oral, 10 mg
    10 mg oral tablet weekly
    Other names:
    • Decadron
    • Hemady
Experimental
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)
  • 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.
    Other names:
    • t(11;14) FISH assay
  • Drug: Venetoclax Oral Tablet, 400 mg
    400 mg oral tablet daily
    Other names:
    • Venclexta
  • Drug: Dexamethasone Oral, 20 mg
    20 mg oral tablet weekly
    Other names:
    • Decadron
    • Hemady
Experimental
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
  • 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
Active Comparator
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)
  • Drug: Dexamethasone Oral, 20 mg
    20 mg oral tablet weekly
    Other names:
    • Decadron
    • Hemady
  • 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.
    Other names:
    • Darzalex
  • 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.
    Other names:
    • Treanda
  • Drug: Pomalidomide
    Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.
    Other names:
    • Pomalyst
  • Drug: Ixazomib
    Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.
    Other names:
    • Ninlaro

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Boston Medical Center
617-638-8265

More Details

Status
Recruiting
Sponsor
Rajshekhar Chakraborty, MD

Study Contact

Research Nurse Navigator
212-342-5162
cancerclinicaltrials@cumc.columbia.edu

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.