AzTrials
AzTrials

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypePhase 3NCT02443077

Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

A Phase 3 study testing Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carmustine in people with Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type and Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type, run by National Cancer Institute (NCI) at 281 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This randomized phase III trial studies ibrutinib to see how well it works compared to placebo when given before and after stem cell transplant in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carmustine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
94 participants
Where
281 sitesin 2 countries
Study dates
12 Oct 2016to 23 Dec 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
  • Patients must have paraffin tissue from the diagnostic or relapse biopsy available to be submitted for central pathology review; this review is mandatory prior to registration to confirm eligibility and should be initiated as soon as possible
  • ELIGIBILITY CRITERIA (STEP 1)
  • Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, non-GCB by central review confirmation
  • Patient must be deemed eligible to proceed with high-dose chemotherapy and autologous stem cell transplantation by local transplant center
  • New York Heart Association class I or less; ordinary physical activity does not cause undue fatigue, palpitations, dyspnea, or angina pain; patients 60 years or older must have a left ventricular ejection fraction (LVEF) at rest >= 40% measured by echocardiogram or multi-gated acquisition (MUGA)
Show all 40Show fewer
  • Diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
  • Forced expiratory volume in 1 second (FEV1) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
  • Forced vital capacity (FVC) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless isolated hyperbilirubinemia attributed to Gilbert's syndrome
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
  • Creatinine =< 2.0 mg/dL OR creatinine clearance (calculated clearance permitted) >= 40 mL/min by Cockcroft-Gault formula
  • Prothrombin time (PT)/ international normalized ration (INR) < 1.5 x ULN and partial thromboplastin time (PTT) (activated [a]PTT) < 1.5 x ULN
  • Patient must have progressed or be refractory to prior anthracycline-containing chemotherapy (e.g. rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone [R-CHOP], dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [DA-EPOCH-R], etc)
  • No more than 3 prior regimens for large cell component (e.g. one induction and two salvage therapies); monoclonal antibody alone or involved field/involved site radiotherapy do not count as lines of therapy. Prior CART therapy is allowed and counts as one line of therapy
  • Prior use of ibrutinib is allowed unless patient has had disease progression while receiving ibrutinib
  • Patient must have chemosensitive disease as defined by at least a partial response to salvage therapy at their latest assessment
  • No major surgery =< 7 days prior to registration and no minor surgery =< 3 days prior to registration (with the exception of intravenous access placement, e.g. Hickman or peripherally inserted central catheter [PICC])
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative serum pregnancy test must be obtained within 14 days prior to registration
  • Women of childbearing potential must use adequate contraception from study start to one month after the last dose of protocol therapy; adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence; men must practice complete abstinence or agree to use an adequate contraception method from study start to one month after the last dose of protocol therapy
  • Age >= 18 years
  • Patients should not require chronic use of strong CYP3A inhibitors or strong CYP3A inducers
  • Patients should not require concurrent therapeutic doses of steroids (> 20 mg of prednisone/day or equivalent) unless they need them for the indications; steroids should be discontinued for 14 days before starting protocol treatment
  • Human immunodeficiency virus (HIV) infected patients are eligible provided they meet all other eligibility criteria, and:
  • There is no prior history of acquired immunodeficiency syndrome (AIDS) defining conditions other than historically low CD4+ T-cell count or B-cell lymphoma
  • In the opinion of an expert in HIV disease, prospects for long-term survival are excellent were it not for the diagnosis of lymphoma
  • Use of HIV protease inhibitors as part of the anti-HIV regimen OR as a pharmacologic booster is not allowed
  • Zidovudine is not allowed
  • Once daily combination pills for HIV containing a pharmacologic booster such as cobicistat are not allowed
  • Patients with multi-drug resistant HIV are not eligible
  • Patients cannot have:
  • Active central nervous system or meningeal involvement by lymphoma; patients with a history of central nervous system (CNS) or meningeal involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 91 days prior to registration
  • Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
  • A known bleeding diathesis
  • Requirement for warfarin or similar vitamin K antagonists; these drugs are prohibited 28 days prior to the first treatment and throughout the trial
  • History of stroke or intracranial hemorrhage =< 6 months before treatment
  • Currently active, clinically significant hepatic impairment (Child-Pugh class B or C according to the Child Pugh classification
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or other agents used in study
  • Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment; (PCR positive patients will be excluded)
  • Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2

Who cannot join

None listed.

Trial locations and contacts

281 sites in 2 countries.

281 sites in 2 countries

United States280 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Baton Rouge General Medical Center

    Baton Rouge, Louisiana, 70806

  • Hematology/Oncology Clinic PLLC

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Prisma Health Cancer Institute - Laurens

    Clinton, South Carolina, 29325

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • National Jewish Health-Main Campus

    Denver, Colorado, 80206

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Farmington Health Center

    Farmington, Utah, 84025

  • Simonds-Sinon Regional Cancer Center

    Fitchburg, Massachusetts, 01420

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Vanderbilt-Ingram Cancer Center Cool Springs

    Franklin, Tennessee, 37067

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • National Jewish Health-Western Hematology Oncology

    Golden, Colorado, 80401

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Saint Mary's Hospital and Regional Medical Center

    Grand Junction, Colorado, 81501

  • Grand Valley Oncology

    Grand Junction, Colorado, 81505

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Banner North Colorado Medical Center

    Greeley, Colorado, 80631

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo Cancer Center

    Kalamazoo, Michigan, 49009

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Cancer Center of Kansas-Kingman

    Kingman, Kansas, 67068

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Marshfield Medical Center - Ladysmith

    Ladysmith, Wisconsin, 54848

  • Good Samaritan Hospital - Cancer Centers of Colorado

    Lafayette, Colorado, 80026

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • Cancer Center of Kansas-Liberal

    Liberal, Kansas, 67905

  • Rocky Mountain Cancer Centers-Littleton

    Littleton, Colorado, 80120

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Rocky Mountain Cancer Centers-Sky Ridge

    Lone Tree, Colorado, 80124

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • Banner North Colorado Medical Center - Loveland Campus

    Loveland, Colorado, 80539

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Cancer Center of Kansas-Manhattan

    Manhattan, Kansas, 66502

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Marshfield Medical Center

    Marshfield, Wisconsin, 54449

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Cancer Center of Kansas - McPherson

    McPherson, Kansas, 67460

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

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

    Miami, Florida, 33136

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Saint Patrick Hospital - Community Hospital

    Missoula, Montana, 59802

  • Community Medical Center

    Missoula, Montana, 59804

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Cancer Center of Kansas - Newton

    Newton, Kansas, 67114

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • Cancer and Hematology Centers of Western Michigan - Norton Shores

    Norton Shores, Michigan, 49444

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Saint Alphonsus Cancer Care Center-Ontario

    Ontario, Oregon, 97914

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Upstate Cancer Center at Oswego

    Oswego, New York, 13126

  • Cancer Center of Kansas - Parsons

    Parsons, Kansas, 67357

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Kootenai Clinic Cancer Services - Post Falls

    Post Falls, Idaho, 83854

  • Geisinger Cancer Services-Pottsville

    Pottsville, Pennsylvania, 17901

  • Cancer Center of Kansas - Pratt

    Pratt, Kansas, 67124

  • Utah Valley Regional Medical Center

    Provo, Utah, 84604

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Riverton Hospital

    Riverton, Utah, 84065

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

  • Cancer Center of Kansas - Salina

    Salina, Kansas, 67401

  • Utah Cancer Specialists-Salt Lake City

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Kootenai Clinic Cancer Services - Sandpoint

    Sandpoint, Idaho, 83864

  • Community Medical Center

    Scranton, Pennsylvania, 18510

  • TidalHealth Nanticoke / Allen Cancer Center

    Seaford, Delaware, 19973

  • Pacific Gynecology Specialists

    Seattle, Washington, 98104

  • Swedish Medical Center-Ballard Campus

    Seattle, Washington, 98107

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Kaiser Permanente Washington

    Seattle, Washington, 98112

  • Swedish Medical Center-Cherry Hill

    Seattle, Washington, 98122-5711

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Geisinger Medical Oncology-Selinsgrove

    Selinsgrove, Pennsylvania, 17870

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

  • Providence Regional Cancer System-Shelton

    Shelton, Washington, 98584

  • LSU Health Sciences Center at Shreveport

    Shreveport, Louisiana, 71103

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • South Jordan Health Center

    South Jordan, Utah, 84009

  • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown

    Spokane, Washington, 99204

  • MultiCare Deaconess Cancer and Blood Specialty Center - North

    Spokane, Washington, 99218

  • MultiCare Deaconess Cancer and Blood Specialty Center - Valley

    Spokane Valley, Washington, 99216

  • SSM Health Saint Louis University Hospital

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Saint George Regional Medical Center

    St. George, Utah, 84770

  • Geisinger Medical Group

    State College, Pennsylvania, 16801

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Children's Hospital at Montefiore

    The Bronx, New York, 10467

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

  • Saint Luke's Cancer Institute - Twin Falls

    Twin Falls, Idaho, 83301

  • Vince Lombardi Cancer Clinic-Two Rivers

    Two Rivers, Wisconsin, 54241

  • PeaceHealth Southwest Medical Center

    Vancouver, Washington, 98664

  • Providence Saint Mary Regional Cancer Center

    Walla Walla, Washington, 99362

  • Marshfield Clinic-Wausau Center

    Wausau, Wisconsin, 54401

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Cancer Center of Kansas - Wellington

    Wellington, Kansas, 67152

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Intermountain Health Lutheran Hospital

    Wheat Ridge, Colorado, 80401

  • Associates In Womens Health

    Wichita, Kansas, 67208

  • Cancer Center of Kansas-Wichita Medical Arts Tower

    Wichita, Kansas, 67208

  • Ascension Via Christi Hospitals Wichita

    Wichita, Kansas, 67214

  • Cancer Center of Kansas - Wichita

    Wichita, Kansas, 67214

  • Geisinger Wyoming Valley/Henry Cancer Center

    Wilkes-Barre, Pennsylvania, 18711

  • Christiana Care Health System-Wilmington Hospital

    Wilmington, Delaware, 19801

  • Cancer Center of Kansas - Winfield

    Winfield, Kansas, 67156

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • Marshfield Clinic - Wisconsin Rapids Center

    Wisconsin Rapids, Wisconsin, 54494

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

  • University of Michigan Health - West

    Wyoming, Michigan, 49519

  • Providence Regional Cancer System-Yelm

    Yelm, Washington, 98597

Other trials in United States

Saudi Arabia1 site

  • King Faisal Specialist Hospital and Research Centre

    Riyadh, 11211

Other trials in Saudi Arabia

About this study

Official title: A Randomized Double-Blind Phase III Study of Ibrutinib During and Following Autologous Stem Cell Transplantation Versus Placebo in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma of the Activated B-Cell Subtype

This randomized phase III trial studies ibrutinib to see how well it works compared to placebo when given before and after stem cell transplant in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Before transplant, stem cells are taken from patients and stored. Patients then receive high doses of chemotherapy to kill cancer cells and make room for healthy cells. After treatment, the stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Ibrutinib is a drug that may stop the growth of cancer cells by blocking a protein that is needed for cell growth. It is not yet known whether adding ibrutinib to chemotherapy before and after stem cell transplant may help the transplant work better in patients with relapsed or refractory diffuse large B-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the ability of ibrutinib to improve 24-month progression free survival (PFS) compared to placebo in patients with non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) as determined by immunohistochemistry (IHC).

SECONDARY OBJECTIVES:

  1. To evaluate the ability of ibrutinib to improve overall survival (OS) compared to placebo.

II. To evaluate the ability of ibrutinib to improve progression free survival (PFS) compared to placebo.

III. To evaluate the ability of ibrutinib to improve post-transplant response rates compared to placebo.

IV. To evaluate time to hematopoietic recovery in the two arms. V. To evaluate the safety and tolerability of ibrutinib compared to placebo. VI. To evaluate the incidence of secondary malignancies in the two arms. VII. To evaluate immune reconstitution in the two arms.

CORRELATIVE SCIENCE OBJECTIVES:

  1. To assess whether pre-autologous hematopoietic stem cell transplantation (AutoHCT) positive fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) is associated with inferior 24-month PFS as well as PFS and OS.

II. To assess whether pre-AutoHCT FDG-PET results are differentially associated with 24-month PFS, PFS and OS in the ibrutinib versus placebo arms.

III. To evaluate the application of the Lugano criteria and change in quantitative measurements between pre-AutoHCT and post AutoHCT (e.g. delta standard uptake variable [SUV], %SUV decline and %metabolic tumor volume [MTV] decline, and other available applicable quantitative measurements) to assess the association between changes in these variables and outcomes, such as PFS and OS.

IV. To assess whether the GSTT1 null polymorphism is correlated with pulmonary toxicity after BCNU (carmustine)-containing conditioning regimens as part of autologous stem cell transplantation.

  1. To assess whether other polymorphisms in the BCNU metabolism pathway or BCNU damage repair pathway(s) are associated with pulmonary toxicity after BCNU-containing conditioning regimens as part of autologous stem cell transplantation.

VI. To evaluate whether any of the proposed deoxyribonucleic acid (DNA) polymorphisms are associated with other toxicities.

VII. To assess whether DLBCL subtype based on the lymphoma subtyping test (LST) is associated with 24-month PFS, PFS, and OS with ibrutinib compared to placebo in patients treated on this protocol.

VIII. To assess whether activating mutations in the BCR pathway are associated with response to ibrutinib and with clinical outcomes in patients treated on this protocol.

IX. To assess whether there are any phenotypic associations with IHC markers (particularly MYC protein expression level) and presence of these mutations.

  1. To assess whether BCL2, MYC, and Ki67 expression by IHC affect clinical outcomes in patients treated on this protocol.

XI. To assess whether translocations in MYC with or without BCL2 and BC6 have poor outcomes in patients treated on this protocol and whether ibrutinib modifies the prognosis.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

CONDITIONING REGIMEN:

ARM I: Investigators may choose to use either the BEAMi (carmustine, etoposide, cytarabine, melphalan, ibrutinib) or CBVi (cyclophosphamide, carmustine, etoposide, ibrutinib) regimen.

BEAMi: Patients receive ibrutinib orally (PO) on days -6 to -1, carmustine intravenously (IV) over 2 hours on day -6, etoposide IV twice daily (BID) over 1-2 hours and cytarabine IV BID over 1-2 hours on days -5 to -2, and melphalan IV over 20-30 minutes on day -1. Optionally, if a day of rest is planned, patients may receive BEAMi on days -7 to -2.

CBVi: Patients receive ibrutinib PO on days -6 to -1, carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. Optionally, if a day of rest is planned, patients may receive CBVi on days -7 to -2.

ARM II: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.

TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.

CONTINUATION REGIMEN:

ARM I: Beginning 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.

After completion of treatment, patients are followed up every 6 months for up to 60 months from registration.

Being tested
Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation, Carmustine, Cyclophosphamide, Cytarabine

What participants receive

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

  • Autologous Bone Marrow TransplantationProcedure or surgery

    Also called ABMT, Autologous Blood and Marrow Transplantation, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation

    Undergo autologous hematopoietic progenitor cells or bone marrow transplant

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

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

    Undergo autologous hematopoietic progenitor cells or bone marrow transplant

  • CarmustineDrug

    Also called BCNU, Becenum, Becenun, BiCNU

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MelphalanDrug

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

    Given IV

  • Pharmacogenomic StudyOther

    Also called PHARMACOGENOMIC

    Correlative studies

  • Placebo AdministrationOther

    Given PO

Study groups in NCT02443077
Study groupRoleWhat they receive
Arm I (ibrutinib, chemotherapy, autoHCT)ExperimentalCONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen. BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV BID over 1-2 hours and cytarabine IV BID over 1-2 hours on days -5 to -2, and melphalan IV over 20-30 minutes on day -1. CBVi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Autologous Bone Marrow Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Etoposide; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Other: Pharmacogenomic Study
Arm II (placebo, chemotherapy, autoHCT)Placebo comparatorCONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I. TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Receives: Procedure: Autologous Bone Marrow Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Other: Pharmacogenomic Study; Other: Placebo Administration

What is being measured

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

  1. 24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization

    Will be assessed using the Lugano classification.

    Measured: Time between registration and disease progression or death, whichever comes first, assessed at 24 months

Secondary outcomes (7)

  1. Overall Survival (OS)

    For each arm, the distribution of OS will be estimated using the Kaplan-Meier method. OS will be compared between the two arms using the log-rank test and Cox regression method adjusting for the known predictors.

    Measured: The time between randomization and death from any cause, assessed up to 5 years (60 months)

  2. Time to Hematopoietic Engraftment

    Will be defined as platelet count greater than or equal to 20,000/uL following nadir.

    Measured: First day of one week without platelet transfusion, assessed up to 5 years

  3. PFS

    For each arm, the distribution of PFS will be estimated using the Kaplan-Meier method. PFS will be compared between the two arms using the log-rank test and Cox regression method adjusting for the known predictors.

    Measured: Time between registration and disease progression or death, whichever comes first, assessed up to 5 years (60 months)

  4. Response Rate Using the Lugano Classification

    The metabolic response proportion following AutoHCT will be compared between the two arms using chi-squared test.

    Measured: Up to 60 months

  5. Treatment-related Mortality

    Treatment-related mortality will be summarized using contingency tables.

    Measured: Up to 60 months

  6. Incidence of Hematologic Toxicity of Ibrutinib Therapy

    Hematologic toxicity will be summarized using contingency tables.

    Measured: Up to 60 months

  7. Incidence of Secondary Malignancies

    Incidence of secondary malignancies will be summarized using contingency tables.

    Measured: Up to 60 months

Timeline

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

  1. First posted13 May 2015 (estimated)
  2. Study start12 Oct 2016
  3. Primary completion10 Jun 2024
  4. Study completion23 Dec 2026 (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
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
94 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02443077
Sponsor's protocol ID
NCI-2015-00668
Other IDs
NCI-2015-00668, BMT CTN 1201, A051301, A051301, A051301, U10CA180821
Status last verified
Jun 2026
First submitted
11 May 2015
Last updated
31 Jul 2026
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carmustine in people with Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type and Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type, run by National Cancer Institute (NCI) at 281 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 281 sites in United States, Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization (time frame: Time between registration and disease progression or death, whichever comes first, assessed at 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02443077.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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