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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT01728259
Date of registration: 13/11/2012
Prospective Registration: Yes
Primary sponsor: Barbara Ann Karmanos Cancer Institute
Public title: First-line Pomalidomide, Bortezomib, and Dexamethasone For AL Amyloidosis or LCDD
Scientific title: Phase I Study of Pomalidomide, Bortezomib, and Dexamethasone (PVD) as First-Line Treatment of AL Amyloidosis or Light Chain Deposition Disease
Date of first enrolment: March 2013
Target sample size: 36
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/show/NCT01728259
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1
Countries of recruitment
Canada New Zealand United States
Contacts
Name:     Jeffrey Zonder
Address: 
Telephone:
Email:
Affiliation:  Barbara Ann Karmanos Cancer Institute
Key inclusion & exclusion criteria

Inclusion Criteria:

- 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)

- 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

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Light Chain Deposition Disease
Primary Systemic Amyloidosis
Intervention(s)
Drug: bortezomib
Drug: dexamethasone
Drug: pomalidomide
Other: Laboratory Biomarker Analysis
Primary Outcome(s)
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]
Secondary Outcome(s)
Complete hematologic response rate (hCR) [Time Frame: Up to 28 days]
Organ response rates (heart, liver, kidney) [Time Frame: Up to 28 days]
Overall hematologic response rate (partial response [PR] + complete response [CR]) [Time Frame: Up to 28 days]
Overall survival [Time Frame: From date of registration to date of death, assessed up to 28 days]
Progression free survival [Time Frame: Up to 28 days]
Secondary ID(s)
2011-155
NCI-2012-02228
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Cancer Institute (NCI)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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