A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis
Hematopoietic Malignancies
Unknown Primary
18 Years and older, Male and Female
CR109160 (primary)
NCI-2022-01987
2021-002639-48
54767414AMY2009
Summary
The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide,
Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: immediate daratumumab + VCd
treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic amyloid light
chain (AL) amyloidosis with cardiac involvement and to identify potential mitigation
strategies for cardiac toxicity (cohort 1); to characterize the pharmacokinetics of
subcutaneous (SC) daratumumab, among racial and ethnic minorities, including Black or African
American, with newly diagnosed AL amyloidosis treated with D-VCd (cohort 2).
Objectives
AL amyloidosis is a rare disorder caused by clonal plasma cells that secrete immunoglobulin
light chains that misfold into insoluble amyloid. The insoluble amyloid gets deposited in
vital organs which results in serious and life-threatening organ dysfunction. Daratumumab is
a human immunoglobulin (IgG1K) monoclonal antibody (mAb) that binds with high affinity to a
unique epitope on cluster of differentiation 38 (CD38), a transmembrane glycoprotein. It is a
targeted immunotherapy directed towards tumor cells that overexpress CD38. Participants will
be enrolled into 2 cohorts based on cardiac involvement at baseline for cohort 1 and racial
or ethnic minority with at least one organ involved for cohort 2. This study aims to generate
data on risk factors for cardiac toxicity and to evaluate the cardiac safety of the proposed
treatment regimens and identify potential mitigation strategies for cardiac toxicity such as
deferred VCd treatment, The study will consist of screening phase (up to 28 days) and
treatment phase with up to 24 treatment cycles (each cycle is 28 days). Safety assessment
will include adverse events (AEs), serious adverse events (SAEs), physical examinations,
Eastern Cooperative Oncology Group (ECOG) criteria for performance status, laboratory tests
and vital signs. The overall duration of the study will be up to 3 years and 8 months.
Eligibility
- Cohort 1: Cardiac involvement (amyloid light chain [AL] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved; Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
- A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
- A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer
- Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American
Treatment Sites in Georgia
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