Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Columbia University
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Suzanne Lentzsch, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01222260
First received: October 14, 2010
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

The study is being done to see if the combination of bendamustine and dexamethasone will help people with amyloidosis that has returned after standard treatment. Bendamustine is currently approved by the Food and Drug Administration (FDA) for treatment of chronic lymphocytic leukemia (CLL) and is under clinical development in the United States for the treatment of non-Hodgkin lymphoma (NHL).

Dexamethasone is a synthetic (man-made) steroid with powerful anti-inflammatory effects. It can also alter the body's immune response.


Condition Intervention Phase
AL Amyloidosis
Drug: Bendamustine
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Complete hematologic response (CHR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall hematologic response (OHR) rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Organ response rate (OrRR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Time to Treatment Failure (TTF) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 29
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Bendamustine and Dexamethasone
Drug: Bendamustine

Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle:

CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle

Available to qualifying subjects is the option to dose escalate to dose level (+)1:

120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study)

Drug: Dexamethasone
40 mg orally on days 1, 8, 15, 22 of each cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged ≥ 18 years old
  • Histopathology of amyloidosis or light chain deposition disease based on detection by polarizing microscopy of green bi-refringent material in Congo red-stained tissue specimens or characteristic electron microscopy appearance or immunohistochemical stain with anti-light chain anti-sera
  • Demonstrate measurable disease as defined by one or more of the following:

    • Serum monoclonal protein ≥ 0.5 g/dL by serum electrophoresis
    • Urine monoclonal protein > 200 mg/dL in a 24 hr urine electrophoresis
    • Serum immunoglobulin free light chain ≥ 5 mg/dL AND abnormal serum immunoglobulin kappa lambda free light chain ratio. The difference between involved and uninvolved free light chains should be ≥ 5 mg/dL (dFLC)
    • Demonstrate clonal population of plasma cells in the bone marrow or immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils
  • ECOG performance status of 0, 1, or 2
  • Patients had at least one prior regimen consisting of at least 1 cycle
  • If not previously transplanted, patient should be either ineligible for ASCT, or must have declined the option of ASCT. Patients who have previously had ASCT and have subsequently progressed are eligible, provided other entry criteria are met
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Patients must meet the following laboratory criteria:
  • ANC ≥ 1.5 x 10^9/L
  • Hemoglobin ≥ 9 g/dl (May transfuse PRBC to meet parameter)
  • Platelets ≥ 100x 10^9/L (Must be independent of platelet transfusion)
  • Calculated CrCl greater than or equal to 30 mL/min (Cockcroft-Gault Formula )
  • AST and ALT ≤ 2.5 x upper limit of normal (ULN)
  • Serum bilirubin <1.5 x ULN
  • Serum potassium within normal limits
  • Total serum calcium (corrected for serum albumin) or ionized calcium ≤ ULN

Exclusion Criteria:

  • Patients meeting the criteria for symptomatic MM:

    • lytic lesions on skeletal survey or
    • plasmacytoma Patients meeting International Myeloma Working Group definition of symptomatic myeloma with symptoms only related to associated amyloidosis who would otherwise only meet the criteria for smoldering MM are potentially 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 AV-block, Wenckebach type 2nd degree heart block, or left bundle branch block. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator or an authorized physician sub-investigator as not medically relevant). Note: There is no lower limit of left ventricular ejection fraction below which patients are excluded from participation.
  • Patients with NT-proBNP ≥ 1800nb/L or BNP ≥ 400 ng/L, abnormal cTnT or cTnI
  • Patient has received other investigational drugs within 14 days prior to enrollment
  • Any form of secondary / familial amyloidosis
  • Serious concurrent illness, which in the opinion of the investigator or an authorized physician sub-investigator would interfere with participation in this clinical study,
  • Known HIV infection.
  • Inability to provide informed consent or to comply with the schedule of office and treatment visits
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women(woman not of child-bearing potential is defined as any woman whose menstrual periods have stopped in the past 12 consecutive months or have had a complete hysterectomy or both ovaries surgically removed).
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, low-risk prostate cancer, or cancer after curative treatment.
  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: NCT01222260

Contacts
Contact: Suzanne Lentzsch, MD, PhD sl3440@columbia.edu

Locations
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Stephen Lo    617-638-8274    stephen.lo@bmc.org   
Contact: Salli Fennessey    617-638-8261    salli.fennessey@bmc.org   
Principal Investigator: Vaishali Sanchorawala, MD         
Sub-Investigator: David Seldin, MD, PhD         
Sub-Investigator: Mark Sloan, MD         
Sub-Investigator: Anne Renteria, MD         
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Jodi Jensen    617-636-5558    jjensen@tuftsmedicalcenter.org   
Principal Investigator: Raymond Comenzo, MD         
Sub-Investigator: Andreas Klein, MD         
Sub-Investigator: Kellie Sprague, MD         
Sub-Investigator: Kenneth Miller, MD         
Sub-Investigator: Chakra Chaulagain, MD         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Silva Pregjas, MBA    313-576-8673    pregjas@karmanos.org   
Contact: Christiane Houde, BS    313-576-9381    houdec@karmanos.org   
Principal Investigator: Jeffrey Zonder, MD         
United States, New York
Mt. Sinai Medical Center Recruiting
New York, New York, United States, 10023
Contact: Lisa La    212-241-8615    lisa.la@mssm.edu   
Contact: Talia Goldstein    212-241-7886    talia.goldstein@mssm.edu   
Principal Investigator: Keren Osman, MD         
Sub-Investigator: Sundar Jagannath, MD         
Sub-Investigator: Ajai Chari, MD         
Sub-Investigator: Hearn Cho, MD         
Sub-Investigator: Samir Parekh, MD         
Sub-Investigator: Donna Catamero, NP         
Sub-Investigator: Daniel Verina, NP         
Sub-Investigator: Natalie Belostotsky, NP         
Sub-Investigator: Juliet Escalon, NP         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Heather Landau, MD    646-497-9062      
Principal Investigator: Heather Landau, MD         
Sub-Investigator: Hani Hassoun, MD         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Kevin Zikaras    212-304-5485      
Principal Investigator: Suzanne Lentzsch, MD, PhD         
Sub-Investigator: Jordan Schecter, MD         
Sponsors and Collaborators
Columbia University
Cephalon
Investigators
Principal Investigator: Suzanne Lentzsch, MD, PhD Columbia University
  More Information

No publications provided

Responsible Party: Suzanne Lentzsch, MD, Associate Professor of Clinical Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01222260     History of Changes
Other Study ID Numbers: AAAJ7800, 10-012 (PRO10050217)
Study First Received: October 14, 2010
Last Updated: September 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Amyloidosis
Dexamethasone
Bendamustine
Relapsed AL Amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bendamustine
Nitrogen Mustard Compounds
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 02, 2014