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

NCT05250973 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: CR10916054767414AMY20092021-002639-482023-507069-25-00
• Study Type: interventional
• Target: 151
• Locations: 10 countries
• Sites: 46

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).

Conditions

Amyloidosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (13)

• Overall Complete Hematologic Response (HemCR) Rate

  Up to Cycle 12 or Month 12 (whichever occurs later)

• HemCR Rate

  At 6 months

• Very Good Partial Response (VGPR) or Better Rate

  Up to Cycle 12 or Month 12 (whichever occurs later)

• Time to HemCR or (VGPR or Better)

  Up to Cycle 12 or Month 12 (whichever occurs later)

• Duration of Response (HemCR and VGPR or Better)

  Up to Cycle 12 or Month 12 (whichever occurs later)

Study Arms (3)

Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd)

EXPERIMENTAL

Participants with newly diagnosed systemic amyloid light chain (AL) amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive daratumumab 1800 milligrams (mg) subcutaneously (SC) starting on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Cohort1 (Arm B): Daratumumab + Deferred VCd

EXPERIMENTAL

Participants with newly diagnosed systemic AL amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive SC daratumumab 1800mg on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (Cyclophosphamide 300 mg/m\^2 either orally or IV, Bortezomib 1.3 mg/m\^2 SC or IV, Dexamethasone 40 mg weekly either orally or IV) starting at Cycle 4 Day 1, weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles (Cycle 9 Day 22).

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Cohort 2: Daratumumab + VCd

EXPERIMENTAL

Participants with racial and ethnic minorities, including Black or African American participants, with newly diagnosed AL amyloidosis will receive SC injection of daratumumab 1800 mg SC on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab will be administered subcutaneously.

Also known as: JNJ-54767414

Cohort 2: Daratumumab + VCd; Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd); Cohort1 (Arm B): Daratumumab + Deferred VCd

Cyclophosphamide DRUG

Cyclophosphamide will be administered either orally or IV.

Cohort 2: Daratumumab + VCd; Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd); Cohort1 (Arm B): Daratumumab + Deferred VCd

Bortezomib DRUG

Bortezomib will be administered by SC injection or IV.

Cohort 2: Daratumumab + VCd; Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd); Cohort1 (Arm B): Daratumumab + Deferred VCd

Dexamethasone DRUG

Dexamethasone will be administered orally or IV.

Cohort 2: Daratumumab + VCd; Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd); Cohort1 (Arm B): Daratumumab + Deferred VCd

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (46)

City of Hope

Duarte, California, 91010, United States

Location

Yale

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Wake Forest University - Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

Ohio Health Research Institute

Columbus, Ohio, 43214, United States

Location

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

VCU Medical Center

Richmond, Virginia, 23219, United States

Location

University of Washington

Seattle, Washington, 02118-30002, United States

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

University Health Network UHN Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Peking University People's Hospital

Beijing, 100044, China

Location

West China Hospital Si Chuan University

Chengdu, 610041, China

Location

First affiliated Hospital of Zhejiang University

Hangzhou, 310003, China

Location

Ruijin Hospital Shanghai Jiao Tong University

Shanghai, 200025, China

Location

CHU de Limoges

Limoges, 87042, France

Location

Centre hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

CHU De Poitiers

Poitiers, 86000, France

Location

CHU Rangueil

Toulouse, 31400, France

Location

Charite Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Universitaetsklinikum Heidelberg Medizinische Klinik V

Heidelberg, 69120, Germany

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

Università Degli Studi Di Napoli Federico Ii

Naples, 80131, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''

Roma, 00161, Italy

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Hospital Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Clinica Univ. de Navarra 1

Madrid, 28027, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Leicester Royal Infirmary - Haematology

Leicester, LE1 5WW, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Amyloidosis

Interventions

daratumumab; Cyclophosphamide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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.

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: February 22, 2022
• Study Start: March 1, 2022
• Primary Completion: May 30, 2025
• Study Completion (Estimated): October 22, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); GB (2); CN (5); NL (3); ES (6); US (16); FR (4); DE (3); GR (1); IT (3)