Clinical Trial 21858

• Overview

  Study Title:

  A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants with Amyloid Light Chain AL Amyloidosis

  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).

  Objective:

  Primary Objective- 1. Cohort 1: to characterize cardiac safety of different D-VCd treatment regimens (Arm A: immediate daratumumab + VCd treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic AL amyloidosis with cardiac involvement and to identify potential mitigation strategies (monitoring of cardiac health/performance via ECG, echocardiography [ECHO], 6 min walk test, biomarkers [TroponinT, HS TroponinT, and NT-proBNP] to inform clinical mitigation strategies alongside comparison of different treatment schedules) for cardiac toxicity. Cohort 2: To characterize the PK of SC daratumumab, among racial and ethnic minorities, including Black or African American, with newly diagnosed systemic AL amyloidosis treated with D-VCd.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Therapy (NOS)

  Medications:

  Bortezomib (); Daratumumab (Darzalex); Dexamethasone (); Diphenhydramine (); PS-341 (Bortezomib); Velcade (Bortezomib); acetaminophen (); cyclophosphamide (); cytoxan (cyclophosphamide)

• Inclusion Criteria

  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
  • Other criteria apply

• Exclusion Criteria

  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: (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 (> 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
  • Other criteria apply

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