A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis

  • STATUS
    Recruiting
  • End date
    Nov 18, 2025
  • participants needed
    150
  • sponsor
    Janssen Research & Development, LLC
Updated on 12 July 2022
cyclophosphamide
dexamethasone
daratumumab
amyloid deposition

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).

Description

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.

Details
Condition Amyloidosis
Treatment cyclophosphamide, Dexamethasone, Bortezomib, Daratumumab
Clinical Study IdentifierNCT05250973
SponsorJanssen Research & Development, LLC
Last Modified on12 July 2022

Eligibility

Yes No Not Sure

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 3 months after discontinuation of daratumumab, whichever is longer
Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American

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 per International Myeloma Working Group (IMWG) Criteria
Participant received any of the following therapies
treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less
vaccinated with an investigational vaccine (except for COVID-19) live, attenuated or replicating viral vector vaccines within 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
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