Daratumumab for the Treatment of Patients With AL Amyloidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02841033
• Date of registration: 14/06/2016
• Prospective Registration: Yes
• Primary sponsor: Boston Medical Center
• Public title: Daratumumab for the Treatment of Patients With AL Amyloidosis
• Scientific title: A Phase I-II Trial of Daratumumab for the Treatment of Patients With AL Amyloidosis
• Date of first enrolment: March 20, 2017
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02841033
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Vaishali Sanchorawala, MD
• Affiliation: Boston Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histological diagnosis of primary systemic (AL) amyloidosis:

1. At least one tissue demonstrating positive Congo Red staining with characteristic
apple green birefringence AND

2. 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 < 2.0
mg/dL; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 3x
upper limit of normal (ULN).

- Must have an absolute neutrophil count =1000/mm3, hemoglobin =7.5 g/dL, and platelet
count =50×109/L

Exclusion Criteria:

- • Renal Insufficiency (CrCL <20mL/min), calculated by Cockcroft-Gault Equation
Creatinine Clearance = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72) Equation
parameters such as sex have two or more discrete values that may be used in the
calculation. The numbers in the parentheses, e.g. (1), represent the values that will
be used. The default unit of measure for weight is kilograms. Please verify that the
correct unit of measure has been selected.

- Mayo clinic cardiac biomarker stage IIIb

- Evidence of significant cardiovascular conditions as specified below:

- B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide (NT-ProBNP) >
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 < 90 mm Hg.

- left ventricular ejection fraction (LVEF) <40%

- Overt multiple myeloma (>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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

AL Amyloidosis

Intervention(s)

Drug: daratumumab

Primary Outcome(s)

Assess frequency and severity of side effects and number of patients who respond to treatment [Time Frame: 3 months]

Secondary Outcome(s)

time to next treatment [Time Frame: 5 years]

Assess organ responses based on standard criteria included in protocol [Time Frame: 3 months]

Assess hematologic response based on blood and urine testing using standard criteria [Time Frame: 3 months]

Secondary ID(s)

54767414AMY2002

H-35360

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Janssen Pharmaceuticals