Daratumumab for the Treatment of Patients With AL Amyloidosis

Inclusion Criteria

• Histological diagnosis of primary systemic (AL) amyloidosis:
• At least one tissue demonstrating positive Congo Red staining with characteristic apple green birefringence AND
• Evidence of a clonal plasma cell dyscrasia:

i. Monoclonal protein in the serum and/or urine by immunofixation electrophoresis AND/OR ii. Abnormal serum free light chain assay AND/OR iii. Clonal plasma cell population in the bone marrow demonstrated by immunohistochemistry, flow cytometry or in situ hybridization AND

c. Evidence of organ involvement other than carpal tunnel syndrome. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.

• Must have relapsed after or been refractory to at least one prior treatment regimen of proven efficacy in the treatment of AL amyloidosis
• Must be > 18 years of age.
• Must have a performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
• Must have adequate hepatic function as evidenced by serum bilirubin values 8500 ng/L (Mayo Stage IIIb patients are excluded)
• New York Heart Association (NYHA) classification IIIB or IV heart failure
• Unstable Angina, Arrhythmia, prolonged corrected QT (QTc) interval, symptomatic orthostatic hypotension, or supine systolic blood pressure 30% bone marrow plasmacytosis, extensive (>2) lytic lesions, or hypercalcemia).
• Plan for autologous stem cell transplant in the six months prior to study drug (stem cell collection is permitted during the first six months of study treatment)
• Any form of secondary or familial (ATTR) amyloidosis
• The presence or history of another malignancy is not allowed except for the following:
• adequately treated basal cell or squamous cell skin cancer,
• in situ cervical cancer,
• adequately treated Stage I or II cancer from which the patient is currently in complete remission, any other cancer from which the patient has been disease-free for 5 years.
• Known to be Human Immunodeficiency Virus (HIV) positivity.
• Pregnant or nursing women. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume at one second (FEV1) <50% of predicted normal. Note that forced expiratory volume at one second FEV1 testing is required for patients suspected of having COPD.
• Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification