AzTrials
AzTrials

AL AmyloidosisPhase 3NCT06022939

Comparing Dara-VCD Chemotherapy Plus Stem Cell Transplant to Dara-VCD Chemotherapy Alone for People Who Have Newly Diagnosed AL Amyloidosis

A Phase 3 study testing Autologous Hematopoietic Stem Cell Transplantation, Biopsy and Biospecimen Collection in people with AL Amyloidosis, run by SWOG Cancer Research Network at 117 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial summary

This phase III trial compares the effect of adding a stem cell transplant with melphalan after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with newly diagnosed amyloid light chain (AL) amyloidosis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AL Amyloidosis
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Biopsy and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
338 participants
Where
117 sitesUnited States
Study dates
1 Jul 2024to 29 Oct 2030
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • STEP 1: Participants must have systemic AL amyloidosis which is biopsy proven and includes histologically-confirmed by positive Congo red stain with green birefringence on polarized light microscopy, OR characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence). If there is question regarding diagnosis, consult study chairs prior to registration
  • STEP 1: Participants must have measurable disease within 28 days prior to treatment if initiated prior to registration or within 28 days of registration as defined by at least one of the following:
  • Positive monoclonal serum immunofixation electrophoresis
  • Positive monoclonal urine immunofixation electrophoresis
  • Monoclonal plasma cells in bone marrow In addition, participants must also have a difference between the involved and uninvolved free light chain (dFLC) >= 2 mg/dL
  • STEP 1: Participants may receive up to one cycle (or 28 days) of therapy prior to enrollment. If a patient receives >= 75% of 1 cycle of protocol identical Dara-VCD, this will be considered 1 cycle of protocol induction. Any patient who receives less than 75% of 1 cycle of Dara-VCD or non-protocol therapy will still be eligible but will be treated per protocol. If protocol identical therapy is initiated prior to enrollment, this treatment is not continued but rather treatment is dictated per protocol
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  • STEP 1: Participants may be receiving chronic corticosteroids if they are being given for disorders other than AL amyloidosis or myeloma
  • STEP 1: Participant must be >= 18 years old
  • STEP 1: Participant must have Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0, 1, or 2 (PS = 3 may be allowed if secondary to neuropathy)
  • STEP 1: Participant must have a complete medical history and physical exam within 28 DAYS prior to registration
  • STEP 1: Participants must be willing to undergo high dose chemotherapy and autologous stem cell transplantation if they are randomized to the arm receiving high dose chemotherapy and autologous stem cell transplantation
  • STEP 1: Participants must be eligible to receive high dose chemotherapy with melphalan at a dose of 200 mg/m^2 or 140 mg/m^2 (200 mg/m^2 is highly encouraged but not mandated). Transplant eligibility criteria are included in the general eligibility criteria listed below:
  • Participant must have a supine systolic blood pressure (BP) >= 90 mmHg (at registration step-1, this may by supported by midodrine
  • Participant must have non-severe cardiac AL (meeting all the below criteria) as defined by:
  • N-terminal proB-type natriuretic peptide (NT proBNP) < 5000 (if no NTproBNP, brain natriuretic peptide [BNP] must be available and < 400)
  • Troponin T (TnT) < 0.06. If not available, one of the following two criteria must be met:
  • High sensitivity troponin (hsTnT) T < 75 or troponin I < 0.1ng/dL
  • New York Heart Association (NYHA) I or II
  • Cardiac ejection fraction (EF) >= 40%
  • STEP 1: Hemoglobin >= 8.0 g/dL (> 5 mmol/L); red blood cell transfusion allowed up to 7 day prior to registration (within 28 days prior to registration) (NOTE: Growth factor support granulocyte colony-stimulating factor [G-CSF] is permitted per institutional guidelines)
  • STEP 1: Leukocytes >= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 1: Absolute neutrophil count >= 1.0 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 1: Platelets >= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 1: Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
  • STEP 1: Direct bilirubin =< 2.0 mg/dL (within 28 days prior to registration)
  • STEP 1: Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 1: Alkaline phosphatase =< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 1: Participants must have a serum creatinine =< the institutional (I)ULN OR measured OR calculated creatinine clearance >= 30 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to registration
  • STEP 1: If peripheral neuropathy is present at diagnosis, participants must be grade 2 (moderate symptoms; limiting instrumental activity of daily living [ADL]) or less
  • STEP 1: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
  • STEP 1: Participants must not be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
  • STEP 1: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
  • STEP 1: Participants must not have concurrent multiple myeloma as defined by the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells in the bone marrow, or hypercalcemia. Participants will not be excluded solely based on the presence of plasma cells > 10% in the bone marrow unless the plasma cell percentage exceeds >60%
  • STEP 1: Participants must not have known allergies to any of the study drugs
  • STEP 1: Participants must not have had a major surgery within 14 days prior to registration and be fully recovered from surgery completed within 14 days prior to registration
  • STEP 1: Participants must not have a known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal
  • STEP 1: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
  • STEP 1: Participants must not have either moderate or severe persistent asthma within the past 2 years), or currently have uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)
  • STEP 1: Participants must not have uncontrolled diabetes within 28 days prior to registration
  • STEP 1: Participants must not have uncontrolled blood pressure and hypertension within 14 days prior to registration. Participants must have a supine systolic BP of >= 90 mmHg
  • STEP 1: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • STEP 1: Participants must not have received vaccination with live attenuated vaccines within 28 days prior to Registration to Step 1
  • STEP 1: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment
  • STEP 1: Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
  • STEP 1: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwestern Oncology group (SWOG) Specimen Tracking System
  • STEP 1: Participants must agree to have blood, bone marrow core biopsy and aspirate, and fat pad biopsy specimens submitted for minimal residual disease assessment and future exploratory studies
  • STEP 1: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms in English, Spanish and French must participate in the patient-reported outcomes and quality of life
  • STEP 2: Participants must have met all eligibility criteria for Step-1 registration
  • STEP 2: Participants must have achieved at least a partial response
  • STEP 2: Participants must continue receiving at least one of study drugs (bortezomib, cyclophosphamide, or daratumumab and hyaluronidase-fihj) if another study drug (daratumumab and hyaluronidase-fihj, cyclophosphamide, or bortezomib) has been discontinued due to adverse events. Note: daratumumab and hyaluronidase-fihj cannot be permanently discontinued
  • STEP 2: Participants must have completed induction therapy
  • STEP 2: Participants must be registered to Step 2 within 42 days of cycle 3, day 28 of induction therapy
  • STEP 2: Participants must plan to initiate their assigned consolidation therapy within 8 weeks after randomization
  • STEP 2: Participants must not have experienced a MOD-PFS event
  • STEP 2: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 may be allowed if secondary to neuropathy)
  • STEP 2: Participant must have a complete medical history and physical exam within 28 days prior to registration
  • STEP 2: Participants must be willing to undergo high dose chemotherapy and autologous stem cell transplantation if they are randomized to the arm receiving high dose chemotherapy and autologous stem cell transplantation
  • STEP 2: Participants randomized to Arm 2 must be willing and able to return to a participating treatment center for their assigned treatment after transplant. Note that participants need not to have a direct relationship with the transplant center in order to register
  • STEP 2: Participants must be eligible to receive high dose chemotherapy with melphalan at a dose of 200 mg/m^2 or 140 mg/m^2 (200 mg/m^2 is highly encouraged but not mandated). Transplant eligibility criteria are included in the general eligibility criteria listed below:
  • Patient must have a supine systolic BP >= 90 mmHg (at registration step-1, this may not by supported by midodrine)
  • Patient must have non-severe cardiac AL as defined by:
  • NT proBNP <5000 (if no NTproBNP, BNP must be available and < 400 pg/mL) (within 14 days prior to registration step-2)
  • TnT < 0.06. If not available, one of the following two criteria must be met (within 14 days prior to registration step-2)
  • hsTnT <75 or troponin I < 0.1ng/dL
  • NYHA I or II (within 14 days prior to registration step-2)
  • Cardiac EF >= 40% (within 14 days prior to registration step-2)
  • STEP 2: Hemoglobin > 8.0 g/dL (> 5 mmol/L); red blood cell transfusion allowed up to 7 days prior to registration (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 2: Leukocytes >= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 2: Absolute neutrophil count >= 1.0 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 2: Platelets >= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 2: Total bilirubin =< 1.5 times the institutional ULN unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
  • STEP 2: Direct bilirubin =< 2.0 mg/dL (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 2: AST/ALT =< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 2: Alkaline phosphatase =< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 2: Participants must have a serum creatinine =< the IULN OR calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
  • STEP 2: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment
  • STEP 2: Participants randomized to the ASCT arm must be able to have at least 2.0 x 10^6 CD34 cells/kg collected
  • STEP 2: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms in English, Spanish and French must participate in the patient-reported outcomes and quality of life
  • STEP 3: Participants must have met all eligibility criteria for Step-1 and Step-2 registration
  • STEP 3: Participants must not have had daratumumab and hyaluronidase-fihj permanently discontinued during induction or consolidation
  • STEP 3: Participants must have completed induction and consolidation therapy
  • STEP 3: Participants must be registered to Step 3 within the following time frames:
  • If randomized to Arm 1 Dara-VCD consolidation: within 28 days of completion of 3 cycles of consolidation therapy
  • If randomized to Arm 2 high dose chemotherapy and autologous stem cell transplantation: within 180 days following initiation of stem cell transplantation
  • STEP 3: Participants must not have experienced a MOD-PFS event
  • STEP 3: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 is allowed if secondary to neuropathy)
  • STEP 3: Participants must have a complete medical history and physical exam within 28 DAYS prior to registration
  • STEP 3: Hemoglobin > 8.0 g/dL (> 5 mmol/L); red blood cell transfusion allowed up to 7 days prior to registration (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 3: Leukocytes >= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 3: Absolute neutrophil count >= 1.0 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 3: Platelets >= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional guidelines)
  • STEP 3: Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
  • STEP 3: Direct bilirubin =< 2.0 mg/dL (within 28 days prior to registration)
  • STEP 3: AST/ALT =< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 3: Alkaline phosphatase =< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration)
  • STEP 3: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
  • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Who cannot join

None listed.

Trial locations and contacts

117 sites in 1 country. Contact the study team or a site near you to ask about taking part.

117 sites in 1 country

United States117 sites, 116 recruiting

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

    Site Public Contact, 515-241-3305

    Seema Harichand-Herdt

    Recruiting

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

    Site Public Contact, 800-865-1125, CancerAnswerLine@med.umich.edu

    Matthew J. Pianko

    Recruiting

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

    Site Public Contact, 888-946-7447

    Jonathan L. Kaufman

    Recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Site Public Contact, 404-778-1868

    Jonathan L. Kaufman

    Recruiting

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

    Site Public Contact, 630-978-6212, RCMC_Cancer_Research@rush.edu

    Priyank P. Patel

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

    Site Public Contact, 954-461-2180

    James E. Hoffman

    Recruiting

  • Houston Methodist San Jacinto Hospital

    Baytown, Texas, 77521

    Site Public Contact, protocols@swog.org

    Carrie H. Yuen

    Recruiting

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

    Site Public Contact, 402-559-6941, unmcrsa@unmc.edu

    Sarah A. Holstein

    Recruiting

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

    Site Public Contact, 301-319-2100

    Christin Destefano

    Recruiting

  • Boston Medical Center

    Boston, Massachusetts, 02118

    Site Public Contact, 617-638-8265

    Vaishali Sanchorawala

    Recruiting

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

    Site Public Contact, 980-201-6360, kashah@novanthealth.org

    Raymond Thertulien

    Recruiting

  • University of Illinois

    Chicago, Illinois, 60612

    Site Public Contact, 312-355-3046

    Ana Maria Avila Rodriguez

    Recruiting

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Keith E. Stockerl-Goldstein

    Recruiting

  • Case Western Reserve University

    Cleveland, Ohio, 44106

    Site Public Contact, 800-641-2422, CTUReferral@UHhospitals.org

    Timothy E. O'brien

    Recruiting

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

    Site Public Contact, 515-241-3305

    Seema Harichand-Herdt

    Recruiting

  • Baptist Memorial Hospital and Cancer Center-Collierville

    Collierville, Tennessee, 38017

    Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org

    Brion V. Randolph

    Recruiting

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

    Site Public Contact, 614-788-3860, Jennifer.Sexton@ohiohealth.com

    Yvonne A. Efebera

    Recruiting

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

    Site Public Contact, 212-639-7592

    Heather J. Landau

    Recruiting

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Springs

    Coral Springs, Florida, 33065

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Keith E. Stockerl-Goldstein

    Recruiting

  • Houston Methodist Cypress Hospital

    Cypress, Texas, 77429

    Site Public Contact, 346-356-1413, irb@houstonmethodist.org

    Carrie H. Yuen

    Recruiting

  • Carle at The Riverfront

    Danville, Illinois, 61832

    Site Public Contact, 800-446-5532, Research@Carle.com

    Priyank P. Patel

    Recruiting

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

    Site Public Contact, 570-271-5251, HemonCCTrials@geisinger.edu

    Joseph P. Lynch

    Recruiting

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

    Site Public Contact, 515-241-6727

    Seema Harichand-Herdt

    Recruiting

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

    Site Public Contact, 515-241-3305

    Seema Harichand-Herdt

    Recruiting

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

    Site Public Contact, 515-241-3305

    Seema Harichand-Herdt

    Recruiting

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Andrew Kin

    Recruiting

  • Henry Ford Hospital

    Detroit, Michigan, 48202

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Site Public Contact, 800-826-4673, becomingapatient@coh.org

    Michael A. Rosenzweig

    Recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27710

    Site Public Contact, 888-275-3853

    Cristiana C. Chase

    Recruiting

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Andrew Kin

    Recruiting

  • CTCA at Western Regional Medical Center

    Goodyear, Arizona, 85338

    Site Public Contact, 623-207-3000

    Tibor J. Kovacsovics

    Recruiting

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

    Site Public Contact, 920-433-8889, WI_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

    Site Public Contact, 920-433-8889, wi_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Smilow Cancer Hospital Care Center at Greenwich

    Greenwich, Connecticut, 06830

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

    Site Public Contact, 212-639-7592

    Heather J. Landau

    Recruiting

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Hollywood

    Hollywood, Florida, 33021

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • Houston Methodist Hospital

    Houston, Texas, 77030

    Site Public Contact, 713-790-2700

    Carrie H. Yuen

    Recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 877-632-6789, askmdanderson@mdanderson.org

    Jing Christine Ye

    Recruiting

  • Methodist Willowbrook Hospital

    Houston, Texas, 77070

    Site Public Contact, protocols@swog.org

    Carrie H. Yuen

    Recruiting

  • Houston Methodist West Hospital

    Houston, Texas, 77094

    Site Public Contact, 832-522-2873

    Carrie H. Yuen

    Recruiting

  • Novant Health Cancer Institute - Huntersville

    Huntersville, North Carolina, 28078

    Site Public Contact, 980-201-6360, kashah@novanthealth.org

    Raymond Thertulien

    Recruiting

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Polina Bellman

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Site Public Contact, 877-467-3411

    Michael A. Rosenzweig

    Recruiting

  • Allegiance Health

    Jackson, Michigan, 49201

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Muhammad Umair Mushtaq

    Recruiting

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

    Site Public Contact, 608-775-2385, cancerctr@gundersenhealth.org

    David E. Marinier

    Recruiting

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Andrew Kin

    Recruiting

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Matthew J. Brunner

    Recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Matthew J. Brunner

    Recruiting

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • Loyola University Medical Center

    Maywood, Illinois, 60153

    Site Public Contact, 708-226-4357

    Patrick A. Hagen

    Recruiting

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

    Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org

    Brion V. Randolph

    Recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

    Site Public Contact, 212-639-7592

    Heather J. Landau

    Recruiting

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Site Public Contact, 414-805-3666

    Anita D'Souza

    Recruiting

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

    Site Public Contact, 212-639-7592

    Heather J. Landau

    Recruiting

  • Novant Health Cancer Institute - Mooresville

    Mooresville, North Carolina, 28117

    Site Public Contact, 980-201-6360, kashah@novanthealth.org

    Raymond Thertulien

    Recruiting

  • Houston Methodist Saint John Hospital

    Nassau Bay, Texas, 77058

    Site Public Contact, protocols@swog.org

    Carrie H. Yuen

    Recruiting

  • Yale University

    New Haven, Connecticut, 06520

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

    Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Rajshekhar Chakraborty

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Heather J. Landau

    Recruiting

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

    North Miami, Florida, 33181

    Site Public Contact, kginnity@med.miami.edu

    James E. Hoffman

    Recruiting

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

    Site Public Contact, 920-433-8889, WI_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

    Site Public Contact, 402-559-5600

    Sarah A. Holstein

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Site Public Contact, 402-559-6941, unmcrsa@unmc.edu

    Sarah A. Holstein

    Recruiting

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Polina Bellman

    Recruiting

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Baptist Memorial Hospital and Cancer Center-Oxford

    Oxford, Mississippi, 38655

    Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org

    Brion V. Randolph

    Recruiting

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 215-349-8245, PMCancerResearch@pennmedicine.upenn.edu

    Adam Waxman

    Recruiting

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

    Site Public Contact, 215-600-9151, ONCTrialNow@jefferson.edu

    Adam F. Binder

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

    Site Public Contact, 305-243-2647

    James E. Hoffman

    Recruiting

  • Providence Portland Medical Center

    Portland, Oregon, 97213

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Oregon Health and Science University

    Portland, Oregon, 97239

    Active, not recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Site Public Contact, 855-776-0015

    Taxiarchis Kourelis

    Recruiting

  • University of Rochester

    Rochester, New York, 14642

    Site Public Contact, 585-275-5830

    Frank C. Passero

    Recruiting

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Regions Hospital

    Saint Paul, Minnesota, 55101

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • United Hospital

    Saint Paul, Minnesota, 55102

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Saint Vincent Hospital Cancer Center at Sheboygan

    Sheboygan, Wisconsin, 53081

    Site Public Contact, 920-433-8889, wi_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Sheboygan Physicians Group

    Sheboygan, Wisconsin, 53081

    Site Public Contact, 920-433-8889, wi_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Baptist Memorial Hospital and Cancer Center-Desoto

    Southhaven, Mississippi, 38671

    Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org

    Brion V. Randolph

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Keith E. Stockerl-Goldstein

    Recruiting

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Keith E. Stockerl-Goldstein

    Recruiting

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Keith E. Stockerl-Goldstein

    Recruiting

  • Smilow Cancer Hospital Care Center at Long Ridge

    Stamford, Connecticut, 06902

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • Saint Vincent Hospital Cancer Center at Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235-1495

    Site Public Contact, 920-433-8889, wi_research_admin@hshs.org

    Matthew L. Ryan

    Recruiting

  • Houston Methodist Sugar Land Hospital

    Sugar Land, Texas, 77479

    Site Public Contact, 281-242-2873

    Carrie H. Yuen

    Recruiting

  • Houston Methodist The Woodlands Hospital

    The Woodlands, Texas, 77385

    Site Public Contact, 713-790-2700, hmthewoodlands@houstonmethodist.org

    Carrie H. Yuen

    Recruiting

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

    Site Public Contact, 203-785-5702, canceranswers@yale.edu

    Terri L. Parker

    Recruiting

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

    Site Public Contact, UACC-IIT@uacc.arizona.edu

    Muhammad Husnain

    Recruiting

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

    Site Public Contact, UACC-IIT@uacc.arizona.edu

    Muhammad Husnain

    Recruiting

  • Carle Cancer Center

    Urbana, Illinois, 61801

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

    Site Public Contact, 202-444-2223

    Kimberley Doucette

    Recruiting

  • UI Health Care Mission Cancer and Blood - Waukee Clinic

    Waukee, Iowa, 50263

    Site Public Contact, 515-241-3305

    Seema Harichand-Herdt

    Recruiting

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Philip Kuriakose

    Recruiting

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Muhammad Umair Mushtaq

    Recruiting

  • Geisinger Wyoming Valley/Henry Cancer Center

    Wilkes-Barre, Pennsylvania, 18711

    Site Public Contact, 570-271-5251, HemonCCTrials@geisinger.edu

    Joseph P. Lynch

    Recruiting

  • Novant Health Forsyth Medical Center

    Winston-Salem, North Carolina, 27103

    Site Public Contact, 336-718-8335, pjordan@novanthealth.org

    Franklin L. Chen

    Recruiting

  • Henry Ford Wyandotte Hospital

    Wyandotte, Michigan, 48192

    Site Public Contact, nhay@hfhs.org

    Philip Kuriakose

    Recruiting

Other trials in United States

About this study

Official title: A Phase III, Randomized Study of Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone (Dara-VCD) Induction Followed by Autologous Stem Cell Transplant or Dara-VCD Consolidation and Daratumumab Maintenance in Patients With Newly Diagnosed AL Amyloidosis

This phase III trial compares the effect of adding a stem cell transplant with melphalan after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to replace the blood forming cells that were destroyed by the chemotherapy. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs, such as cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly diagnosed AL amyloidosis.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare major organ deterioration progression-free survival between participants randomized to the autologous stem cell transplant (ASCT) and non-ASCT arms of this study.

SECONDARY OBJECTIVES:

  1. To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT arms of this study.

II. To compare rates of cardiac and renal organ responses between participants randomized to the ASCT and non-ASCT arms of this study.

III. To compare rates of cardiac and renal organ progression between participants randomized to the ASCT and non-ASCT arms of the study.

IV. To compare the frequency and severity of toxicities between participants randomized to the ASCT and non-ASCT arms of this study.

  1. To compare minimal residual disease (MRD) negativity rates between participants randomized to the ASCT and non-ACST arms of this study.

ADDITIONAL OBJECTIVES:

  1. To compare the best overall hematologic response rates between participants randomized to the ASCT and non-ASCT arms of this study.

II. To compare rates of hematologic complete response (CR) and very good partial response, following completion of consolidation therapy between participants randomized to the ASCT and non-ASCT arms of this study, post-consolidation.

III. To compare hematologic progression-free survival between participants randomized to the ASCT and non-ASCT arms of this study.

IV. To compare time to next treatment between participants randomized to the ASCT and non-ASCT arms of the study.

  1. To evaluate utilization of delayed ASCT in participants randomized to the non-ASCT arm of the study.

TRANSLATIONAL MEDICINE PRIMARY OBJECTIVES:

  1. To compare MRD negativity rates from bone marrow aspirates via next generation flow cytometry (NGF) between the ASCT and non-ASCT arms of this study post-consolidation.

II. To bank specimens for future use.

TRANSLATIONAL MEDICINE EXPLORATORY OBJECTIVES:

  1. To evaluate MRD negativity rates at post-induction, and compare MRD negativity rates at 12 months post-consolidation from bone marrow aspirates via NGF between participants randomized to the ASCT and non-ASCT arms of this study.

II. To investigate the association of achieving MRD negativity at any point (post-induction, post-consolidation, or 12 months post-consolidation) via NGF from bone marrow aspirates with major organ deterioration-progression free survival (MOD-PFS).

III. To investigate the association of achieving sustained MRD negativity (MRD negative at two consecutive measurements -- post-induction, post-consolidation, and 12 months post-consolidation) via NGF from bone marrow aspirates with MOD-PFS.

QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:

  1. To compare patient-reported physical function following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the Patient Reported Outcomes Measurement Information System (PROMIS)-29+2 Profile version (v) 2.1 physical function sub-scale.

QOL SECONDARY OBJECTIVES:

  1. To compare patient-reported fatigue following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the PROMIS-29 fatigue subscale.

II. To compare longitudinal changes in physical function using the PROMS-29+2 between participants randomized to the ASCT and non-ASCT arms.

QOL EXPLORATORY OBJECTIVES:

  1. To assess baseline symptom burden in AL amyloidosis patients prior to induction therapy using the PROMIS-29+2.

II. To compare mean scores of symptom scales using the PROMIS-29+2 following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms.

III. To compare mean scores of functional scales using the PROMIS-29+2, following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms.

IV. To explore whether longitudinal changes in symptoms, functioning, and overall heath related quality of life (HRQoL) as assessed by the PROMIS-29 +2 (version 2.1) differ according to treatment group and, separately, according to baseline cardiac or renal involvement using interaction tests between participants randomized to the ASCT and non-ASCT arms.

  1. To compare health utility indices using the PROMIS preference score (PROPr) between patients randomized to the ASCT and non-ASCT arms.

PATIENT REPORTED OUTCOME (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) PRIMARY OBJECTIVE:

  1. To compare patient reported symptoms regarding treatment emergent adverse events of interest using the Patient Reported Outcome CTCAE (PRO-CTCAE) Measurement System between patients randomized to the ASCT and non-ASCT arms of this study.

OUTLINE:

INDUCTION: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide orally (PO) or intravenously (IV), and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.

CONSOLIDATION: Patients who achieve an overall response of partial response or better after 3 cycles of Dara-VCD are randomized to 1 of 2 arms.

ARM I: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.

ARM II: Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.

MAINTENANCE: Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.

After completion of study treatment, patients are followed up every 3 or 6 months up to 4 years after registration.

Conditions
AL Amyloidosis
Being tested
Autologous Hematopoietic Stem Cell Transplantation, Biopsy, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy
Medical subject headings
Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo fat pad biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and urine specimen collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given SC

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given PO or IV

  • Daratumumab and Hyaluronidase-fihjDrug

    Also called DARA Co-formulated with rHuPH20, DARA/rHuPH20, Daratumumab + rHuPH20, Daratumumab with rHuPH20

    Given SC

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO or IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET-CT

  • Stem Cell IsolationProcedure or surgery

    Also called Isolation, Stem Cell, Stem Cell Collection, Stem Cell Recovery

    Undergo stem cell collection

  • Survey AdministrationOther

    Ancillary study

Study groups in NCT06022939
Study groupRoleWhat they receive
Consolidation Arm I (Chemotherapy)Active comparatorPatients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Daratumumab and Hyaluronidase-fihj; Drug: Dexamethasone; Procedure: Echocardiography; Other: Survey Administration
Consolidation Arm II (Chemotherapy, ASCT)ExperimentalPatients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography; Drug: Melphalan; Procedure: Stem Cell Isolation; Other: Survey Administration
Induction (Chemotherapy)ExperimentalPatients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI or PET-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Bortezomib; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Daratumumab and Hyaluronidase-fihj; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Survey Administration
Maintenance (daratumumab and hyaluronidase-fihj)ExperimentalPatients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Daratumumab and Hyaluronidase-fihj; Procedure: Echocardiography; Other: Survey Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major organ deterioration progression-free survival (PFS)

    Will be performed using a stratified log-rank test for comparison between study arms. The analyses will be stratified according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 versus [vs.] 2-3), hematological response following 2 cycles of daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) induction (partial response [PR] or worse vs. very good partial response [VGPR] or better), and presence of t(11;14) by interphase fluorescence in situ hybridization [iFISH] (yes vs. no). All eligible participants will be considered in analyses of the primary endpoint, according to their assigned arm at randomization.

    Measured: From date of randomization (Step 2 registration) to date of first documentation of hematologic progression, cardiac organ progression, renal organ progression, or death due to any cause, assessed up to 4 years

Secondary outcomes (11)

  1. Overall survival

    Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. [VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: From randomization to date of death due to any cause, assessed up to 4 years

  2. Hematologic PFS

    Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: From randomization (Step 2 registration) to date of first documentation of hematologic progression, or death due to any cause, assessed up to 4 years

  3. Cardiac and renal organ response rates

    Progression will be defined based on objective evidence of worsening of organ dysfunction due to AL amyloid. Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: Up to 4 years

  4. Measurable residual disease (MRD) negativity rate

    Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: From baseline to off treatment follow-up (prior to progression) or 12 months post consolidation

  5. Best overall hematologic response

    Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years

  6. Overall hematologic response rate

    Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years

  7. Rate of complete response

    Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: Up to 4 years

  8. Rate of very good complete response or better

    Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).

    Measured: Up to 4 years

  9. Time to next treatment

    Will be analyzed using the cumulative incidence competing risks method.

    Measured: From date of initial registration (Step 1) to date of initiation of next line of therapy, assessed up to 4 years

  10. Change in patient reported health quality of life (QOL)

    Will use the PROMIS-29+2 (version 2.1) to compare the physical function between participants in the ASCT vs. non-ASCT arm.

    Measured: From baseline to post-maintenance, approximately 24 months

  11. Incidence of adverse events

    Participant-reported toxicity will be examined using Patient Reported Outcome-Common Terminology Criteria for Adverse Events.

    Measured: Up to the end of maintenance therapy, approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2023
  2. Study start1 Jul 2024
  3. Primary completion29 Jul 2030 (estimated)
  4. Study completion29 Oct 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
338 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06022939
Sponsor's protocol ID
S2213
Other IDs
NCI-2023-04234, S2213, S2213, U10CA180888
Status last verified
Sep 2025
First submitted
11 Aug 2023
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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