Clinical trial NCT05250973: A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis
Official title: A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Amyloidosis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-02-22
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants of Cohort 1 will be randomized to either Arm A or Arm B of Cohort 1 in a 2:1 ratio. For Cohort 2, participants will be enrolled without randomization.
Primary purpose: TREATMENT

Brief summary: 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 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
* 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

Primary outcomes:
measure: Number of Participants with Cardiac Events of Any Toxicity Grade
timeFrame: Up to 12 months
measure: Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) of Daratumumab
timeFrame: Cycle 3 Day 1 predose (each cycle is of 28 days)
Secondary outcomes:
measure: Overall Complete Hematologic Response (HemCR) Rate
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: HemCR Rate
timeFrame: At 6 months
measure: Very Good Partial Response (VGPR) or Better Rate
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Time to HemCR or (VGPR or Better)
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Duration of Response (HemCR and VGPR or Better)
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Organ Response Rate (OrRR)
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Overall Survival (OS)
timeFrame: Until Cycle 12 or Month 12 (whichever occurs later)
measure: Time to Subsequent Therapy
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Serum Concentration of Daratumumab
timeFrame: Up to 3 years
measure: Number of Participants with Antibodies to Daratumumab
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Number of Participants with Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20)
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
measure: Change from Baseline in Clinical Signs and Symptoms Score of Cardiac AL Amyloidosis
timeFrame: Up to Cycle 12 or Month 12 (whichever occurs later)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital/Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University
state: Georgia
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University - Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network UHN Princess Margaret Cancer Centre
state: Ontario
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People s Hospital
city: Chengdu
country: China
facility: West China Hospital Si Chuan University
city: Hangzhou
country: China
facility: First affiliated Hospital of Zhejiang University
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiao Tong University
city: Limoges Cedex
country: France
facility: CHU de Limoges
city: Pierre Benite cedex
country: France
facility: Centre hospitalier Lyon-Sud
city: Poitiers
country: France
facility: CHU De Poitiers
city: Toulouse
country: France
facility: CHU Rangueil
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg Medizinische Klinik V
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Napoli
country: Italy
facility: Università Degli Studi Di Napoli Federico Ii
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Hospital Maastricht University Medical Center
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Clinica Univ. de Navarra
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary - Haematology
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: