First-line Pomalidomide, Bortezomib, and Dexamethasone For AL Amyloidosis or LCDD

NCT01728259 | Terminated Phase 1 DMC

• 1 other identifier: 2011-155
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 5

Brief Summary

This phase I trial studies the side effects and best dose of pomalidomide and bortezomib when given together with dexamethasone in treating patients with amyloid light-chain amyloidosis or light chain deposition disease. Biological therapies, such as pomalidomide, may stimulate the immune system in different ways and stop abnormal cells from growing. Bortezomib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth. Giving pomalidomide and bortezomib together with dexamethasone may be an effective treatment for amyloid light-chain amyloidosis or light chain deposition disease

Conditions

Light Chain Deposition Disease; Primary Systemic Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose defined as the dose level before 2 of 6 patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  28 days

Secondary Outcomes (5)

• Complete hematologic response rate (hCR)

  Up to 28 days

• Overall hematologic response rate (partial response [PR] + complete response [CR])

  Up to 28 days

• Organ response rates (heart, liver, kidney)

  Up to 28 days

• Overall survival

  From date of registration to date of death, assessed up to 28 days

• Progression free survival

  Up to 28 days

Study Arms (1)

Treatment (pomalidomide, bortezomib, and dexamethasone)

EXPERIMENTAL

Patients receive pomalidomide PO on days 1-21; bortezomib IV or SC on days 1, 8, and 15; and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: pomalidomide; Drug: bortezomib; Drug: dexamethasone; Other: Laboratory Biomarker Analysis

Interventions

pomalidomide DRUG

Given PO

Also known as: CC-4047

Treatment (pomalidomide, bortezomib, and dexamethasone)

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (pomalidomide, bortezomib, and dexamethasone)

dexamethasone DRUG

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (pomalidomide, bortezomib, and dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pomalidomide, bortezomib, and dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent form
• Able to adhere to protocol requirements
• Histologically confirmed AL or LCDD (any time prior to screening)
• Up to 1 cycle of prior therapy allowed (maximum of 120 mg total dexamethasone (or equivalent amount of prednisone), 4 days of melphalan, and/or 4 doses of velcade; at least 4 wks has to have had passed since last dose of melphalan, 2 wks since last velcade or glucocorticoid dose
• Measurable light chain elevation, as defined by:
• A difference between the involved immunoglobulin free light chain and uninvolved light chain and uninvolved light chain (dFLC) of \>= 5 mg/dL AND abnormal serum immunoglobulin kappa lambda free light chain ratio
• EXCEPTION: during the DOSE ESCALATION PORTION of the study only, a measurable M-protein (\>= 0.5 g/dL) on serum protein electrophoresis (SPEP) or a measurable urinary light chain (\>= 200 mg/24 hrs) by urine protein electrophoresis (UPEP) without a dFLC meeting the above criteria is acceptable; subjects without a dFLC \>= 5 mg/dL treated at the MTD will not count towards the expansion cohort
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry
• Demonstrated clonal population of plasma cells in the bone marrow or positive immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils
• NTproBNP \< 8500 pg/mL
• Absolute neutrophil count \>= 1000/mm\^3
• Platelet count \>= 75,000/mm\^3
• Serum creatinine =\< 2.5 mg/dL
• Total bilirubin =\< 1.5 mg/dL
• AST(SGOT) and ALT(SGPT) =\< 3 x upper limit of normal (ULN)

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking pomalidomide)
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 28 days of baseline
• Known hypersensitivity reaction or history of desquamating rash related to thalidomide or lenalidomide
• Known hypersensitivity to bortezomib, boron, or any of the other agents utilized in this protocol
• Patient has \>= grade 3 peripheral sensory neuropathy or \>= grade 2 painful sensory neuropathy within 14 days before enrollment; (NOTE: patient with peripheral neuropathy \[PN\] that was previously this severe but is currently improved due to ongoing therapy \[e.g., gabapentin or amitriptyline\] may be eligible)
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including 1st degree atrioventricular (AV)-block, Wenckebach type 2nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant); note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
• Concurrent use of other anti-cancer agents or treatments
• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C
• Meets criteria for symptomatic multiple myeloma, defined as:
• \>= 10% monoclonal plasma cells in the marrow AND ANY OF THE FOLLOWING:
• Biopsy-confirmed plasmacytoma
• Lytic bone lesion(s)
• Hypercalcemia without other explanation

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead

Study Sites (5)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118-2393, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

pomalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Jeffrey Zonder

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 19, 2012
• Study Start: March 1, 2013
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

US (4); CA (1)