Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Suzanne Lentzsch, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01222260
First received: October 14, 2010
Last updated: June 27, 2016
Last verified: June 2016
  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, and to to estimate the partial hematologic response rate (PHR).

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:
  • Partial hematologic response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

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

Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Subjects with AL will receive 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)
Other Names:
  • Bendamustine Hydrochloride
  • Treanda ®
Drug: Dexamethasone
40 mg orally on days 1, 8, 15, 22 of each cycle
Other Name: Decadron

Detailed Description:

Systemic light-chain amyloidosis (AL) is a protein conformation disorder due to a clonal plasma cell dyscrasia. There are no established and approved second-line therapies for patients with systemic AL amyloidosis who fail initial melphalan-based treatment, be it high-dose melphalan with stem cell transplant or oral melphalan and dexamethasone (MDex). Therefore new treatments are needed for those who fail initial therapy and for those who initially respond but subsequently relapse.

Therapy of AL is generally based on treatment regimens used in multiple myeloma (MM). Bendamustine achieves partial response with relapsed/refractory MM. Based on this high anti-MM activity, we anticipate that bendamustine will also be very active in clonal plasma cell disorder associated with AL.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Locations
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10023
Columbia University
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Columbia University
Cephalon
Investigators
Principal Investigator: Suzanne Lentzsch, MD, PhD Columbia University
  More Information

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: June 27, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Undecided

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 Hydrochloride
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
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 July 21, 2016