AzTrials
AzTrials

Light Chain Deposition DiseasePhase 1NCT01728259

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

A Phase 1 study testing pomalidomide, bortezomib and dexamethasone in people with Light Chain Deposition Disease and Primary Systemic Amyloidosis, run by Barbara Ann Karmanos Cancer Institute at 5 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pomalidomide, bortezomib and dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
5 sitesin 2 countries
Study dates
Mar 2013to 31 Oct 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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)
  • All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program
  • Disease free of prior malignancies for > or = 2 years with exception of treated basal cell or squamous cell carcinoma of the skin. Carcinoma "in situ" of the cervix or breast, or low-risk localized prostate cancer does not outright exclude patients, but such cases need to be discussed with Dr. Zonder prior to enrollment.
  • Females of childbearing potential (FCBP) must have negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Able to take aspirin (ASA;81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin), unless baseline prothrombin time [PT] or partial thromboplastin time [PTT] is >= 1.5 ULN, in which case thromboprophylaxis not required

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • Boston University School of Medicine

    Boston, Massachusetts, 02118-2393

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Phase I Study of Pomalidomide, Bortezomib, and Dexamethasone (PVD) as First-Line Treatment of AL Amyloidosis or Light Chain Deposition Disease

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. Establish the maximum tolerated dose (MTD) of the combination of pomalidomide, bortezomib, and dexamethasone (PVD) to take forward in a subsequent phase 2 study.

SECONDARY OBJECTIVES:

  1. Obtain a preliminary assessment of efficacy of PVD regimen as initial treatment of amyloid light-chain (AL) or light chain deposition disease (LCDD).

OUTLINE: This is a dose-escalation study of pomalidomide and bortezomib.

Patients receive pomalidomide orally (PO) on days 1-21; bortezomib intravenously (IV) 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.

After completion of study treatment, patients are followed up at least every 3 months.

Being tested
pomalidomide, bortezomib, dexamethasone, Laboratory Biomarker Analysis
Medical subject headings
Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pomalidomideDrug

    Also called CC-4047

    Given PO

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01728259
Study groupRoleWhat they receive
Treatment (pomalidomide, bortezomib, and dexamethasone)ExperimentalPatients 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.
Receives: Drug: pomalidomide; Drug: bortezomib; Drug: dexamethasone; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 28 days

Secondary outcomes (5)

  1. Complete hematologic response rate (hCR)

    Will be estimated and reported with 95% confidence intervals.

    Measured: Up to 28 days

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

    Measured: Up to 28 days

  3. Organ response rates (heart, liver, kidney)

    Organ responses will be tabulated and reported for all patients with cardiac, renal, hepatic, and/or neurologic involvement by amyloidosis.

    Measured: Up to 28 days

  4. Overall survival

    Will be estimated and reported with 95% confidence interval.

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

  5. Progression free survival

    Will be estimated and reported with 95% confidence interval.

    Measured: Up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2012 (estimated)
  2. Study startMar 2013
  3. Primary completion31 Oct 2018
  4. Study completion31 Oct 2018

Why it stopped: FDA placed the study on a clinical hold, due to the concerns by the FDA and Health Canada, Celgene decided to permanently close the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01728259
Sponsor's protocol ID
2011-155
Status last verified
May 2023
First submitted
13 Nov 2012
Last updated
9 May 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pomalidomide, bortezomib and dexamethasone in people with Light Chain Deposition Disease and Primary Systemic Amyloidosis, run by Barbara Ann Karmanos Cancer Institute at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: FDA placed the study on a clinical hold, due to the concerns by the FDA and Health Canada, Celgene decided to permanently close the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01728259.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in