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Active, not recruitingNCT02443077Updated Jul 31, 2026Results posted

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

A Phase 3 interventional study of Autologous Bone Marrow Transplantation and Autologous Hematopoietic Stem Cell Transplantation in Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type and Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type, sponsored by National Cancer Institute (NCI). Active, not recruiting at 281 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-31.

Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
94
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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). 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:

I. 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:

I. 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:

I. 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.

V. 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.

X. 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.

02

Conditions studied

  • Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type
03

In context

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • 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)
  • 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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
94 participants (actual)

Study arms

  • Experimental
    Arm I (ibrutinib, chemotherapy, autoHCT)

    CONDITIONING 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.

    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

  • Placebo comparator
    Arm II (placebo, chemotherapy, autoHCT)

    CONDITIONING 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.

    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

Interventions

  • ProcedureAutologous Bone Marrow Transplantation

    Undergo autologous hematopoietic progenitor cells or bone marrow transplant

    Also known as: ABMT, Autologous Blood and Marrow Transplantation, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation

  • ProcedureAutologous Hematopoietic Stem Cell Transplantation

    Undergo autologous hematopoietic progenitor cells or bone marrow transplant

    Also known as: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous

  • DrugCarmustine

    Given IV

    Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, NSC 409962, NSC409962, SK 27702, SRI 1720, WR 139021, WR-139021, WR139021

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Frindovyx, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

  • DrugCytarabine

    Given IV

    Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

  • DrugEtoposide

    Given IV

    Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

  • DrugIbrutinib

    Given PO

    Also known as: BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765, Imbruvica, PCI 32765, PCI-32765, PCI32765

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugMelphalan

    Given IV

    Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

  • OtherPharmacogenomic Study

    Correlative studies

    Also known as: PHARMACOGENOMIC

  • OtherPlacebo Administration

    Given PO

06

What researchers measure

Primary outcomes

  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.

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

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: Up to 60 months

  5. Treatment-related Mortality

    Treatment-related mortality will be summarized using contingency tables.

    Time frame: Up to 60 months

  6. Incidence of Hematologic Toxicity of Ibrutinib Therapy

    Hematologic toxicity will be summarized using contingency tables.

    Time frame: Up to 60 months

  7. Incidence of Secondary Malignancies

    Incidence of secondary malignancies will be summarized using contingency tables.

    Time frame: Up to 60 months

Other outcomes

  1. Fludeoxyglucose Positron Emission Tomography (FDG-PET) Imaging Results

    PFS and OS will be compared between PET/computed tomography (CT) positive and negative groups using the two-sample log-rank test with a 2-sided alpha of 5%. A Cox regression model will be conducted to regress PFS and OS on PET/CT positivity. Deauville criteria analyses will be conducted with cutoffs at scores of 2 and 3, and quantitative measurements, e.g. delta standard uptake value (SUV), %SUV decline and %MTV decline, in place of the dichotomous FDG-PET/CT outcome. Positive/negative predictive values, sensitivity and specificity of PET/CT further estimated by dichotomizing the PFS and OS at 2 years.

    Time frame: Baseline

  2. GSTT1 Null Allele Expression

    GSTT1 null allele expression will be associated with carmustine toxicity. Quantified using the standard Common Terminology Criteria for Adverse Events and changes in diffusing capacity of the lungs for carbon monoxide from baseline.

    Time frame: Baseline

  3. Single-nuclear Polymorphisms (SNPs) in the BCNU Metabolism or Damage Repair Pathways

    All SNPs will be evaluated for deviation from Hardy-Weinberg. In the absence of a hypothesized effect, analyses will be powered for allele dosing (i.e., additive) effects. The Cochran-Armitage test (for binary endpoints), Jonkheere-Terpstra test (for quantitative traits including biomarker or gene expressions in serum or tumor ribonucleic acid) and the Cox score test (for censored time-to-event outcomes) will be used to quantify marginal associations. Multivariable models, with molecular, clinical and demographic variables, will be constructed using conditional inference trees and random forests.

    Time frame: Baseline

  4. BCR Pathway Mutations

    The mutation of CD79a/b, caspase recruitment domain family, member 11 (CARD11), tumor necrosis factor, alpha-induced protein 3 TNFAIP3), and myeloid differentiation primary response 88 (MYD88) will be associated with each outcome in the ibrutinib arm (Arm A) using the chi-squared test for response rate and the log-rank test for each censored outcome. Similar analyses will be conducted for the placebo arm (Arm B) to show that the association between mutation and the outcomes observed in the ibrutinib arm is not observed in the placebo arm.

    Time frame: Baseline

  5. BCL2, MYC, and Ki67 Expression in Tissue Samples by Immunohistochemistry (IHC)

    The expression of BCL2, MYC, and Ki67 will be analyzed to assess whether they affect clinical outcomes.

    Time frame: Baseline

  6. MYC Translocations

    Translocations in MYC with or without BCL2, and BCL6 will be analyzed to determine whether they are related to poor outcomes and whether ibrutinib modifies the prognosis.

    Time frame: Baseline

07

Results

Posted Sep 30, 2025

Participant flow

Participant flow — Overall Study
MilestoneArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety Cohort
Started45436
Crossover200
Completed1096
Not completed35340

Outcome measures

Primary24-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.

Time frame:
Time between registration and disease progression or death, whichever comes first, assessed at 24 months
Reported as:
Number · proportion of participants
24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization
proportion of participantsArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization0.576 (0.421 to 0.788)0.408 (0.265 to 0.628)
SecondaryOverall 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.

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

Results for this outcome have not been posted.

SecondaryTime to Hematopoietic Engraftment

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

Time frame:
First day of one week without platelet transfusion, assessed up to 5 years
Reported as:
Median · days
Time to Hematopoietic Engraftment
daysArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
Time to Hematopoietic Engraftment14.0 (12.0 to 17.0)14.5 (13.0 to 19.0)
SecondaryPFS

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.

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

Results for this outcome have not been posted.

SecondaryResponse Rate Using the Lugano Classification

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

Time frame:
Up to 60 months
Reported as:
Number · proportion of participants
Response Rate Using the Lugano Classification
proportion of participantsArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
Response Rate Using the Lugano Classification0.590 (0.421 to 0.744)0.553 (0.383 to 0.714)
SecondaryTreatment-related Mortality

Treatment-related mortality will be summarized using contingency tables.

Time frame:
Up to 60 months
Reported as:
Number · participants
Treatment-related Mortality
participantsArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
Disease-related68
Infection40
New Primary10
Other/Unknown24
SecondaryIncidence of Hematologic Toxicity of Ibrutinib Therapy

Hematologic toxicity will be summarized using contingency tables.

Time frame:
Up to 60 months
Reported as:
Count of participants · Participants
Incidence of Hematologic Toxicity of Ibrutinib Therapy
ParticipantsArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
Grade 3 Event69
Grade 4 Event1311
Grade 5 Event00
SecondaryIncidence of Secondary Malignancies

Incidence of secondary malignancies will be summarized using contingency tables.

Time frame:
Up to 60 months
Reported as:
Count of participants · Participants
Incidence of Secondary Malignancies
ParticipantsArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)
Incidence of Secondary Malignancies10
Other pre-specifiedFludeoxyglucose Positron Emission Tomography (FDG-PET) Imaging Results

PFS and OS will be compared between PET/computed tomography (CT) positive and negative groups using the two-sample log-rank test with a 2-sided alpha of 5%. A Cox regression model will be conducted to regress PFS and OS on PET/CT positivity. Deauville criteria analyses will be conducted with cutoffs at scores of 2 and 3, and quantitative measurements, e.g. delta standard uptake value (SUV), %SUV decline and %MTV decline, in place of the dichotomous FDG-PET/CT outcome. Positive/negative predictive values, sensitivity and specificity of PET/CT further estimated by dichotomizing the PFS and OS at 2 years.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedGSTT1 Null Allele Expression

GSTT1 null allele expression will be associated with carmustine toxicity. Quantified using the standard Common Terminology Criteria for Adverse Events and changes in diffusing capacity of the lungs for carbon monoxide from baseline.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedSingle-nuclear Polymorphisms (SNPs) in the BCNU Metabolism or Damage Repair Pathways

All SNPs will be evaluated for deviation from Hardy-Weinberg. In the absence of a hypothesized effect, analyses will be powered for allele dosing (i.e., additive) effects. The Cochran-Armitage test (for binary endpoints), Jonkheere-Terpstra test (for quantitative traits including biomarker or gene expressions in serum or tumor ribonucleic acid) and the Cox score test (for censored time-to-event outcomes) will be used to quantify marginal associations. Multivariable models, with molecular, clinical and demographic variables, will be constructed using conditional inference trees and random forests.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedBCR Pathway Mutations

The mutation of CD79a/b, caspase recruitment domain family, member 11 (CARD11), tumor necrosis factor, alpha-induced protein 3 TNFAIP3), and myeloid differentiation primary response 88 (MYD88) will be associated with each outcome in the ibrutinib arm (Arm A) using the chi-squared test for response rate and the log-rank test for each censored outcome. Similar analyses will be conducted for the placebo arm (Arm B) to show that the association between mutation and the outcomes observed in the ibrutinib arm is not observed in the placebo arm.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedBCL2, MYC, and Ki67 Expression in Tissue Samples by Immunohistochemistry (IHC)

The expression of BCL2, MYC, and Ki67 will be analyzed to assess whether they affect clinical outcomes.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedMYC Translocations

Translocations in MYC with or without BCL2, and BCL6 will be analyzed to determine whether they are related to poor outcomes and whether ibrutinib modifies the prognosis.

Time frame:
Baseline

Results for this outcome have not been posted.

Adverse events

Collected over Up to 60 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (Ibrutinib, Chemotherapy, autoHCT)14/45 (31.1%)22/45 (48.9%)36/45 (80%)
Arm II (Placebo, Chemotherapy, autoHCT)10/43 (23.3%)23/43 (53.5%)38/43 (88.4%)
Safety Cohort3/6 (50%)4/6 (66.7%)6/6 (100%)
Crossover Arm2/2 (100%)1/2 (50%)1/2 (50%)
Most frequent serious events
Showing 10 of 56
Most frequent serious events
EventArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortCrossover Arm
Abdominal painGastrointestinal disorders0/451/430/61/2
Creatinine increasedInvestigations0/450/430/61/2
Metabolism, nutrition disord - Oth specMetabolism and nutrition disorders0/450/430/61/2
Acute kidney injuryRenal and urinary disorders1/451/431/61/2
SepsisInfections and infestations3/452/432/60/2
HypotensionVascular disorders3/451/432/60/2
Atrial fibrillationCardiac disorders0/451/431/60/2
FeverGeneral disorders5/452/431/60/2
Localized edemaGeneral disorders0/450/431/60/2
Infections and infestations - Oth specInfections and infestations2/454/431/60/2
Most frequent other events
Showing 10 of 144
Most frequent other events
EventArm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortCrossover Arm
DiarrheaGastrointestinal disorders29/4528/436/61/2
FatigueGeneral disorders34/4530/436/61/2
NauseaGastrointestinal disorders27/4526/435/61/2
FeverGeneral disorders18/4520/435/60/2
AnorexiaMetabolism and nutrition disorders15/4517/434/60/2
CoughRespiratory, thoracic and mediastinal disorders14/4512/434/60/2
VomitingGastrointestinal disorders13/4514/433/60/2
Lymphocyte count decreasedInvestigations7/456/431/61/2
AnemiaBlood and lymphatic system disorders18/459/431/60/2
Platelet count decreasedInvestigations18/4510/431/60/2

Baseline characteristics

Only randomized arms were analyzed. Safety cohort was excluded per protocol: These patients will not be randomized and will be excluded in the statistical analysis to compare the two arms.

Age, Continuous
Age, Continuous(years)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
Median61 (55 to 67)59 (51 to 66)52.5 (46 to 64)61 (51 to 66)
Sex: Female, Male
Sex: Female, Male(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
Female2020141
Male2523553
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
Hispanic or Latino2305
Not Hispanic or Latino4340689
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
American Indian or Alaska Native0000
Asian1001
Native Hawaiian or Other Pacific Islander0000
Black or African American3104
White3839380
More than one race0000
Unknown or Not Reported3339
Prior Ibrutinib
Prior Ibrutinib(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
Count of participants1001
Time to relapse
Time to relapse(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
<= 12 months (includes refractory)2121547
> 12 months2422147
Type of transplant regimen planned
Type of transplant regimen planned(Participants)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
BEAM4241588
CBV3216
Number of prior lines of chemo
Number of prior lines of chemo(chemo lines)Arm I (Ibrutinib, Chemotherapy, autoHCT)Arm II (Placebo, Chemotherapy, autoHCT)Safety CohortTotal
Median2 (1 to 3)2 (1 to 3)2 (2 to 3)2 (1 to 3)

6 further baseline measures are reported on the registry.

08

Study locations

281 sites
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
  • Anchorage Radiation Therapy Center
    Anchorage, Alaska 99504, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona 85719, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California 92868, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • UCSF Medical Center-Parnassus
    San Francisco, California 94143, United States
  • Rocky Mountain Cancer Centers-Aurora
    Aurora, Colorado 80012, United States
  • The Medical Center of Aurora
    Aurora, Colorado 80012, United States
  • UCHealth University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • Boulder Community Foothills Hospital
    Boulder, Colorado 80303, United States
  • Rocky Mountain Cancer Centers-Boulder
    Boulder, Colorado 80304, United States
  • UCHealth Memorial Hospital Central
    Colorado Springs, Colorado 80909, United States
  • Denver Health Medical Center
    Denver, Colorado 80204, United States
  • National Jewish Health-Main Campus
    Denver, Colorado 80206, United States
  • The Women's Imaging Center
    Denver, Colorado 80209, United States
  • Colorado Blood Cancer Institute
    Denver, Colorado 80218, United States
  • Presbyterian - Saint Lukes Medical Center - Health One
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Midtown
    Denver, Colorado 80218, United States
  • Saint Joseph Hospital - Cancer Centers of Colorado
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Rose
    Denver, Colorado 80220, United States
  • Mountain Blue Cancer Care Center - Swedish
    Englewood, Colorado 80113, United States
  • Swedish Medical Center
    Englewood, Colorado 80113, United States
  • Poudre Valley Hospital
    Fort Collins, Colorado 80524, United States
  • National Jewish Health-Western Hematology Oncology
    Golden, Colorado 80401, United States
  • Saint Mary's Hospital and Regional Medical Center
    Grand Junction, Colorado 81501, United States
  • Grand Valley Oncology
    Grand Junction, Colorado 81505, United States
  • Banner North Colorado Medical Center
    Greeley, Colorado 80631, United States
  • Good Samaritan Hospital - Cancer Centers of Colorado
    Lafayette, Colorado 80026, United States
  • Rocky Mountain Cancer Centers-Littleton
    Littleton, Colorado 80120, United States
  • Rocky Mountain Cancer Centers-Sky Ridge
    Lone Tree, Colorado 80124, United States
  • Banner North Colorado Medical Center - Loveland Campus
    Loveland, Colorado 80539, United States
  • Intermountain Health Lutheran Hospital
    Wheat Ridge, Colorado 80401, United States
  • Smilow Cancer Center/Yale-New Haven Hospital
    New Haven, Connecticut 06510, United States
  • Yale University
    New Haven, Connecticut 06520, United States
  • Beebe Medical Center
    Lewes, Delaware 19958, United States
  • Delaware Clinical and Laboratory Physicians PA
    Newark, Delaware 19713, United States
  • Helen F Graham Cancer Center
    Newark, Delaware 19713, United States
  • Medical Oncology Hematology Consultants PA
    Newark, Delaware 19713, United States
  • Christiana Care Health System-Christiana Hospital
    Newark, Delaware 19718, United States
  • Beebe Health Campus
    Rehoboth Beach, Delaware 19971, United States
  • TidalHealth Nanticoke / Allen Cancer Center
    Seaford, Delaware 19973, United States
  • Christiana Care Health System-Wilmington Hospital
    Wilmington, Delaware 19801, United States
  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    Deerfield Beach, Florida 33442, United States
  • UF Health Cancer Institute - Gainesville
    Gainesville, Florida 32610, United States
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
  • UM Sylvester Comprehensive Cancer Center at Plantation
    Plantation, Florida 33324, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Northside Hospital
    Atlanta, Georgia 30342, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Saint Alphonsus Cancer Care Center-Boise
    Boise, Idaho 83706, United States
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
  • Saint Alphonsus Cancer Care Center-Caldwell
    Caldwell, Idaho 83605, United States
  • Kootenai Health - Coeur d'Alene
    Coeur d'Alene, Idaho 83814, United States
  • Saint Luke's Cancer Institute - Fruitland
    Fruitland, Idaho 83619, United States
  • Saint Luke's Cancer Institute - Meridian
    Meridian, Idaho 83642, United States
  • Saint Alphonsus Cancer Care Center-Nampa
    Nampa, Idaho 83687, United States
  • Saint Luke's Cancer Institute - Nampa
    Nampa, Idaho 83687, United States
  • Kootenai Clinic Cancer Services - Post Falls
    Post Falls, Idaho 83854, United States
  • Kootenai Clinic Cancer Services - Sandpoint
    Sandpoint, Idaho 83864, United States
  • Saint Luke's Cancer Institute - Twin Falls
    Twin Falls, Idaho 83301, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Rush MD Anderson Cancer Center
    Chicago, Illinois 60612, United States
  • University of Illinois
    Chicago, Illinois 60612, United States
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • UC Comprehensive Cancer Center at Silver Cross
    New Lenox, Illinois 60451, United States
  • Cancer Center of Kansas - Chanute
    Chanute, Kansas 66720, United States
  • Cancer Center of Kansas - Dodge City
    Dodge City, Kansas 67801, United States
  • Cancer Center of Kansas - El Dorado
    El Dorado, Kansas 67042, United States
  • Cancer Center of Kansas - Fort Scott
    Fort Scott, Kansas 66701, United States
  • Cancer Center of Kansas-Independence
    Independence, Kansas 67301, United States
  • University of Kansas Cancer Center
    Kansas City, Kansas 66160, United States
  • Cancer Center of Kansas-Kingman
    Kingman, Kansas 67068, United States
  • Lawrence Memorial Hospital
    Lawrence, Kansas 66044, United States
  • Cancer Center of Kansas-Liberal
    Liberal, Kansas 67905, United States
  • Cancer Center of Kansas-Manhattan
    Manhattan, Kansas 66502, United States
  • Cancer Center of Kansas - McPherson
    McPherson, Kansas 67460, United States
  • Cancer Center of Kansas - Newton
    Newton, Kansas 67114, United States
  • Cancer Center of Kansas - Parsons
    Parsons, Kansas 67357, United States
  • Cancer Center of Kansas - Pratt
    Pratt, Kansas 67124, United States
  • Cancer Center of Kansas - Salina
    Salina, Kansas 67401, United States
  • Cancer Center of Kansas - Wellington
    Wellington, Kansas 67152, United States
  • University of Kansas Hospital-Westwood Cancer Center
    Westwood, Kansas 66205, United States
  • Associates In Womens Health
    Wichita, Kansas 67208, United States
  • Cancer Center of Kansas-Wichita Medical Arts Tower
    Wichita, Kansas 67208, United States
  • Ascension Via Christi Hospitals Wichita
    Wichita, Kansas 67214, United States

Showing the first 100 of 281 sites across 2 countries.

09

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 22, 2022
  • Informed consent form · Mar 22, 2022
  • Informed consent form · Mar 22, 2022

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 31, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02443077
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
May 13, 2015
Start date
Oct 12, 2016
Primary completion
Jun 10, 2024
Completion
Dec 23, 2026 (estimated)
Results posted
Sep 30, 2025
Last update
Jul 31, 2026

Study contacts

Charalambos B Andreadis
principal investigator · Alliance for Clinical Trials in Oncology

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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