S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 15 January 2024
• Main ID: NCT03499808
• Date of registration: 09/04/2018
• Prospective Registration: Yes
• Primary sponsor: SWOG Cancer Research Network
• Public title: S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis
• Scientific title: A Phase II Study of Isatuximab (SAR650984) (NSC-795145) for Patients With Previously Treated AL Amyloidosis
• Date of first enrolment: June 6, 2018
• Target sample size: 43
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03499808
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Emma Scott
• Affiliation: SWOG Cancer Research Network

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patient must have relapsed or refractory primary systemic AL amyloidosis,
histologically-confirmed by positive Congo red stain with green by birefringence on
polarized light microscopy, OR characteristic appearance by electron microscopy AND
confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or
immunofluorescence)

- Patient must have measurable disease within 28 days prior to registration; serum beta2
microglobulin, serum quantitative immunoglobulins (immunoglobulin [Ig]G, IgA, and
IgM), serum free kappa and lambda, and serum protein electrophoresis (SPEP) with
M-protein quantification must be obtained within 14 days prior to registration

- Patient must demonstrate a difference in the involved serum free light chains (kappa
or lambda) versus the uninvolved serum free light chain of >= 4.5 mg/dL within 14 days
prior to registration

- Patient must have objective organ involvement defined by ONE (or more) of the
following; all disease for involved organs must be assessed and documented on the AL
baseline tumor assessment form

- Kidney: albuminuria greater than or equal to 500 mg per day on a 24-hour urine
specimen within 35 days prior to registration, OR prior kidney biopsy (at time of
diagnosis) showing amyloid deposition

- Heart: mean left ventricular wall thickness on echocardiogram greater than or
equal to 12 mm in the absence of hypertension or valvular heart disease, OR
N-terminal fragment brain natriuretic protein (NT-pro) brain natriuretic peptide
(BNP) greater than 332 ng/mL provided that patient does not have impaired renal
function (as defined by calculated creatinine clearance less than 25 mL/min)
within 14 days prior to registration, OR prior cardiac biopsy (at time of
diagnosis) showing amyloid deposition with past documented or presently noted
clinical symptoms and signs supportive of a diagnosis of heart failure in the
absence of an alternative explanation for heart failure

- Liver: hepatomegaly (total liver span > 15 cm) as demonstrated by computed
tomography (CT) or magnetic resonance imaging (MRI) within 35 days prior to
registration OR elevated alkaline phosphatase (ALP) greater than 1.5 times the
upper limit of normal within 14 days prior to registration, OR prior liver biopsy
(at time of diagnosis) showing amyloid deposition

- Gastrointestinal tract: prior biopsy showing amyloid deposition AND symptoms such
as GI bleeding or persistent diarrhea (> 4 loose stools/day on most days over a
consecutive 28-day period)

- Autonomic or peripheral nervous system: orthostatic blood pressure, symptoms of
nausea, early satiety, diarrhea or constipation, abnormal sensory and/or motor
findings on neurologic exam, or gastric atony by gastric emptying scan; Note:
pulse and blood pressure must be recorded with the patient supine (lying down),
and then again after at least 1 minute, but less than 3 minutes of standing; this
assessment must be repeated on 2 separate occasions (at least 1 day apart; e.g.
day -3 and day -1) within a 28-day screening period

- Soft tissue: macroglossia, or soft tissue deposits (including lymphadenopathy,
recurrent peri-orbital purpura, peri-articular, skin or other soft tissue)
requiring therapy

- Patients must not have active symptomatic multiple myeloma, as defined by 2015
International Myeloma Working Group (IMWG) criteria (hypercalcemia, renal failure,
anemia, and bone [CRAB] criteria; bone marrow plasmacytosis > 60%); kappa: lambda
ratio > 100 is acceptable only if the clinical symptoms and sign are attributable only
to amyloidosis and not multiple myeloma (hemoglobin [Hgb] < 8 g/dL)

- Patient must be relapsed or refractory to at least one prior line of therapy (such as:
transplant, radiation, or chemotherapy)

- Patients must have completed other systemic therapy >= 14 days or investigational drug
>= 28 days prior to registration, surgery (other than biopsies) >= 21 days prior to
registration, and any autologous stem cell transplant (ASCT) >= 100 days prior to
registration

- Patients must not have received any or supplements which have been known to have some
anti-amyloidogenic effect (such as: doxycycline; curcumin; prednisone; dexamethasone;
epigallocatechin gallate [EGCG]) within 14 days prior to registration

- Patients must not have any known allergies to isatuximab or other monoclonal antibody
therapies

- Patients must not have received daratumumab within 56 days prior to registration nor
have been refractory to daratumumab

- Patients must not be eligible for autologous stem cell transplantation

- Patients must have a complete medical history and physical exam within 14 days prior
to registration

- Within 14 days prior to registration: Total bilirubin =< 2.0 x IULN (institutional
upper limit of the norm) AND

- Within 14 days prior to registration: Serum glutamic-oxaloacetic transaminase
(SGOT)/aspartate aminotransferase (AST) and serum glutamate pyruvate transaminase
(SGPT)/alanine aminotransferase (ALT) =< 4.0 x IULN

- Creatinine clearance (CrCl) >= 25 mL/min, as measured by a 24-hour urine collection or
as estimated by the Cockcroft and Gault formula; the serum creatinine value used in
the calculation must have been obtained within 35 days prior to registration

- Patients must have bone marrow aspirate, including fluorescence in situ hybridization
(FISH) (including: del 17p; t11;14; t4;14, t14;16; and del 13q) and cytogenetic
testing (normal ? XY; and all abnormalities) within 35 days prior to registration;
central pathology analysis will not be required, however the local pathology report
and FISH/cytogenetic data must be submitted in Medidata RAVE

- Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,000
cells/mcl without growth factor support, AND

- Within 14 days prior to registration: Platelets >= 75,000 cells/mcl

- Patients must have hemoglobin >= 8 g/dL within 14 days prior to registration; patients
may have received transfusion if greater than 7 days prior to registration

- New York Heart Association (NYHA) < class IV heart failure

- Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) >= 35% within 35
days prior to registration; and

- NT-proBNP =< 8500 ng/L within 14 days prior to registration




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

Health Condition(s) or Problem(s) studied

Nausea

Primary Systemic Amyloidosis

Early Satiety

Gastrointestinal Hemorrhage

Diarrhea

Hepatomegaly

Recurrent Primary Amyloidosis

Purpura

Lymphadenopathy

Macroglossia

Refractory Primary Amyloidosis

Constipation

Amorphous, Eosinophilic, and Acellular Deposit

Intervention(s)

Other: Laboratory Biomarker Analysis

Biological: Isatuximab

Primary Outcome(s)

Overall confirmed hematologic response rate [Time Frame: Up to 4 years]

Secondary Outcome(s)

Overall survival [Time Frame: From date of registration to date of death due to any cause, assessed up to 4 years]

Progression free survival [Time Frame: From date of registration to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 4 years]

Incidence of adverse events [Time Frame: Up to 4 years]

Organ response [Time Frame: Up to 4 years]

Secondary ID(s)

NCI-2017-01375

U10CA180888

S1702

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)