Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis
Condition: AL Amyloidosis
MeSH terms: Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Intervention: Bendamustine; Dexamethasone
Intervention description: 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); 40 mg orally on days 1, 8, 15, 22 of each cycle
Intervention MeSH terms: Dexamethasone; Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amyloidosis; Dexamethasone; Bendamustine; Relapsed AL Amyloidosis

Summary:

      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).
    

Eligibility 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

          -  Eastern Cooperative Oncology Group (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 autologous
             stem cell transplantation (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:

          -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

          -  Hemoglobin ≥ 9 g/dl (May transfuse packed red blood cells (PRBC) to meet parameter)

          -  Platelets ≥ 100x 10^9/L (Must be independent of platelet transfusion)

          -  Calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min
             (Cockcroft-Gault Formula )

          -  Aspartate transaminase (AST) and alanine transaminase (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 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 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 N-terminal (NT)-proBNP ≥ 1800nb/L or B-type natriuretic peptide (BNP) ≥
             400 ng/L, abnormal cardiac troponin T (cTnT) or cardiac troponin l (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.