Overview
The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: daratumumab + immediate 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).
Eligibility
Inclusion Criteria:
- 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
- Measurable disease at screening defined by one of the following:
Difference between iFLC and uninvolved FLC (dFLC) >= 40mg/L per central laboratory Serum
involved free light chain (iFLC) >= 40 mg/L with an abnormal kappa:lambda ratio Serum
M-protein >= 0.5 g/dL
Exclusion Criteria:
- Prior therapy for systemic AL amyloidosis or multiple myeloma including medications
that target cluster of differentiation 38 (CD38), with the exception of 160
milligrams(mg) dexamethasone or equivalent corticosteroid maximum exposure prior to
randomization/enrollment
- Previous or current diagnosis of symptomatic multiple myeloma, including the presence
of lytic bone disease, plasmacytomas, >=60% plasma cells in the bone marrow, or
hypercalcemia related to myeloma.
- Participant received any of the following therapies:
1. treatment with an investigational drug or used an invasive investigational
medical device within 14 days or at least 5 half-lives, whichever is less;
2. vaccinated with an investigational vaccine (except for COVID-19) live, attenuated
or replicating viral vector vaccines less than (<) 4 weeks prior to
randomization/enrollment. Participants who are taking strong Cytochrome P450
3A4(CYP3A4) inducers must discontinue their use at least 5 half-lives prior to
the first dose of bortezomib
- Stem cell transplantation -Planned stem cell transplant during the first 9 cycles of
protocol therapy are excluded. Stem cell collection during the first 9 cycles of
protocol therapy is permitted
- Grade 2 sensory or Grade 1 painful peripheral neuropathy