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

Amyloidosis Clinical Trial

— AQUARIUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05250973
• Other study ID #: CR109160
• Secondary ID: 2021-002639-4854
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2022
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2027
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Amyloidosis

Intervention

Drug:
• Daratumumab
Daratumumab will be administered subcutaneously.
• Cyclophosphamide
Cyclophosphamide will be administered either orally or IV.
• Bortezomib
Bortezomib will be administered by SC injection or IV.
• Dexamethasone
Dexamethasone will be administered orally or IV.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	University Health Network UHN Princess Margaret Cancer Centre	Toronto	Ontario
China	Peking University First Hospital	Beijing
China	Peking University People s Hospital	Beijing
China	West China Hospital Si Chuan University	Chengdu
China	First affiliated Hospital of Zhejiang University	Hangzhou
China	Ruijin Hospital Shanghai Jiao Tong University	Shanghai
France	CHU de Limoges	Limoges Cedex
France	Centre hospitalier Lyon-Sud	Pierre Benite cedex
France	CHU De Poitiers	Poitiers
France	CHU Rangueil	Toulouse
Germany	Charite Campus Benjamin Franklin	Berlin
Germany	Universitatsklinikum Essen	Essen
Germany	Universitaetsklinikum Heidelberg Medizinische Klinik V	Heidelberg
Greece	Alexandra General Hospital of Athens	Athens
Italy	Università Degli Studi Di Napoli Federico Ii	Napoli
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''	Roma
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Hospital Maastricht University Medical Center	Maastricht
Netherlands	UMC Utrecht	Utrecht
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Clinica Univ. de Navarra	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp Clinico Univ de Salamanca	Salamanca
United Kingdom	Leicester Royal Infirmary - Haematology	Leicester
United Kingdom	University College Hospital	London
United States	Winship Cancer Institute Emory University	Atlanta	Georgia
United States	Boston University Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University Hospital of Cleveland	Cleveland	Ohio
United States	Ohio Health Research Institute	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Smilow Cancer Hospital/Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering	New York	New York
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	VCU Medical Center	Richmond	Virginia
United States	University of Washington	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Germany,  Greece,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Cardiac Events of Any Toxicity Grade	Number of participants with cardiac events of any toxicity grade will be reported.	Up to 12 months
Primary	Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) of Daratumumab	Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.	Cycle 3 Day 1 predose (each cycle is of 28 days)
Secondary	Overall Complete Hematologic Response (HemCR) Rate	Overall HemCR rate is defined as percentage of participants who achieve HemCR during or after the study treatment.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	HemCR Rate	HemCR rate at 6 month is defined as percentage of participants who achieve HemCR at 6 month during or after the study treatment.	At 6 months
Secondary	Very Good Partial Response (VGPR) or Better Rate	Hematologic greater than or equal to (>=) VGPR rate is defined as percentage of participants who achieve hematologic response of VGPR or better.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Time to HemCR or (VGPR or Better)	For participants who achieve HemCR (or >=VGPR), time to HemCR (or >=VGPR) is defined as the time between the date of first study treatment and the first efficacy evaluation at which the participant has met all criteria for hematologic complete response (CR) (or >=VGPR).	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Duration of Response (HemCR and VGPR or Better)	For participants who achieve HemCR (or >=VGPR), duration of HemCR (or >=VGPR) is defined as the time between the date of initial documentation of HemCR (or >=VGPR) to the date of first documented evidence of hematologic progressive disease or death, whichever comes first.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Organ Response Rate (OrRR)	Organ response rate is defined as the percentage of participants who achieve organ response in each corresponding organ (kidney, heart, liver).	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Overall Survival (OS)	OS is measured from the date of first study treatment to the date of the participant's death.	Until Cycle 12 or Month 12 (whichever occurs later)
Secondary	Time to Subsequent Therapy	Time to subsequent therapy for amyloid light chain (AL) amyloidosis is defined as the time from the date of first study treatment to the start date of subsequent AL amyloidosis (non-protocol) treatment.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Number of Participants with Adverse Events (AEs) by Severity	Number of participants with AEs by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Serum Concentration of Daratumumab	Serum samples will be analyzed to determine concentrations of daratumumab.	Up to 3 years
Secondary	Number of Participants with Antibodies to Daratumumab	Number of participants with antibodies to daratumumab will be reported.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Number of Participants with Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20)	Number of participants with antibodies to rHuPH20 will be reported.	Up to Cycle 12 or Month 12 (whichever occurs later)
Secondary	Change from Baseline in Clinical Signs and Symptoms Score of Cardiac AL Amyloidosis	Change from baseline in clinical signs and symptoms score of cardiac AL amyloidosis will be reported.	Up to Cycle 12 or Month 12 (whichever occurs later)