Idelalisib for Immunoglobulin M (IgM)-Associated Primary (AL) Amyloidosis
Condition: Amyloidosis
MeSH terms: Amyloidosis
Intervention: Idelalisib
Intervention description: Idelalisib daily until unacceptable toxicity or disease progression.
Intervention MeSH terms: Idelalisib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: IgM-associated AL amyloidosis

Summary:

      The investigators expect to enroll 15 participants with relapsed or refractory IgM-associated
      AL amyloidosis onto this Phase II clinical trial. Idelalisib will be self-administered orally
      at a dose of 100 mg twice daily (may be increased to 150 mg (one tablet) twice daily after 3
      months at investigator discretion). Participants will be treated until disease progression,
      unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be
      performed every three months until disease progression.
    

Eligibility criteria:

        Inclusion Criteria:

        3.1.1 IgM paraprotein identified on serum immunofixation electrophoresis OR light
        chain-restricted CD20+ lymphoplasmacytic population on biopsy of bone marrow or lymph node
        (identified by H&E/immunohistochemistry or flow cytometry) OR positive myeloid
        differentiation primary response gene 88 (MYD88-L265P) OR CXCR4WHIM mutation (CXCR4
        mutation - warts, hypogammaglobulinemia, infections, myelokathexis) on submitted samples

        3.1.2 Biopsy-proven relapsed or refractory AL amyloidosis

        3.1.3 Age ≥ 18 years

        3.1.4 Eastern Cooperative Oncology Group (ECOG) performance status <2 (see Appendix A.)

        3.1.5 Difference between serum free light chains (FLC) of >30 mg/L or quantifiable IgM
        paraprotein >0.5 g/L

        3.1.6 Participants must have normal organ and marrow function as defined below:

          -  Absolute neutrophil count > 1,000/mm3

          -  Platelets > 50,000/mm3

        3.1.7 Ability to understand and the willingness to sign a written informed consent
        document.

        Exclusion Criteria:

        3.2.1 Previous treatment with idelalisib

        3.2.2 Glomerular filtration rate (GFR) <15 ml/min

        3.2.3 Cardiac biomarker Stage III disease as determined by B-type natriuretic peptide (BNP)
        >100 pg/mL and Troponin-I >0.1 ng/mL (Girnius 2014)

        3.2.4 alanine-aminotransferase (ALT)/aspartate aminotransferase (AST) values >2.5x upper
        limit of normal, Bilirubin >1.5 upper limit of normal (ULN)

        3.2.5 Central nervous system (CNS) malignancy or other active malignancy

        3.2.6 Lactating or pregnant women

        3.2.7 Exposure to another investigational drug within 4 weeks prior to start of study
        treatment

        3.2.8 Ongoing alcohol or drug addiction as determined by investigator

        3.2.9 Amyloid-directed therapy within the past 28 days

        3.2.10 History of Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV)
        (assessed by positive Hepatitis B polymerase chain reaction assay (PCR) or Hepatitis B
        Surface Antigen), and/or Hepatitis C Virus (HCV) infection

        3.2.11 t(11,14) translocation identified on bone marrow cytogenetics or by Fluorescence in
        situ hybridization (FISH)

        3.2.12 Known lytic bone lesions

        3.2.13 Positive cytomegaly virus (CMV) Polymerase chain reaction (PCR)

        3.2.14 Previously untreated AL amyloidosis (Newly diagnosed)

        3.2.15 Unwilling or unable to comply with the protocol