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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01728259
First received: November 13, 2012
Last updated: February 12, 2016
Last verified: February 2016
  Purpose
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

Condition Intervention Phase
Light Chain Deposition Disease
Primary Systemic Amyloidosis
Drug: pomalidomide
Drug: bortezomib
Drug: dexamethasone
Other: Laboratory Biomarker Analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Pomalidomide, Bortezomib, and Dexamethasone (PVD) as First-Line Treatment of AL Amyloidosis or Light Chain Deposition Disease

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete hematologic response rate (hCR) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Will be estimated and reported with 95% confidence intervals.

  • Overall hematologic response rate (partial response [PR] + complete response [CR]) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Organ response rates (heart, liver, kidney) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Organ responses will be tabulated and reported for all patients with cardiac, renal, hepatic, and/or neurologic involvement by amyloidosis.

  • Overall survival [ Time Frame: From date of registration to date of death, assessed up to 28 days ] [ Designated as safety issue: No ]
    Will be estimated and reported with 95% confidence interval.

  • Progression free survival [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Will be estimated and reported with 95% confidence interval.


Estimated Enrollment: 36
Study Start Date: March 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pomalidomide, bortezomib, and dexamethasone)
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
Given PO
Other Name: CC-4047
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01728259

Locations
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Jeffrey V. Matous    720-754-4800    Jeffrey.Matous@HealthONEcares.com   
Principal Investigator: Jeffrey V. Matous         
United States, Massachusetts
Boston University School of Medicine Recruiting
Boston, Massachusetts, United States, 02118-2393
Contact: Vaishali Sanchorawala    617-638-7523    vaishali.sanchorawala@bmc.org   
Principal Investigator: Vaishali Sanchorawala         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Jeffrey A. Zonder    313-576-9363    zonderj@karmanos.org   
Principal Investigator: Jeffrey A. Zonder         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Cristina Gasparetto    919-668-1017    gaspa001@mc.duke.edu   
Principal Investigator: Cristina Gasparetto         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Vishal Kukreti    416-946-4501 ext 4566    Vishal.Kukreti@uhn.ca   
Principal Investigator: Vishal Kukreti         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jeffrey Zonder Barbara Ann Karmanos Cancer Institute
  More Information

Responsible Party: Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01728259     History of Changes
Other Study ID Numbers: 2011-155  NCI-2012-02228 
Study First Received: November 13, 2012
Last Updated: February 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyloidosis
Multiple Myeloma
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Pomalidomide
Bortezomib
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 26, 2016