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

Official record

Identifier

NCT02443077

Recruiting locations

countries

United StatesSaudi Arabia

Interventions studied

Autologous Bone Marrow TransplantationAutologous Hematopoietic Stem Cell TransplantationCarmustineCyclophosphamideCytarabineEtoposideIbrutinibLaboratory Biomarker AnalysisMelphalanPharmacogenomic StudyPlacebo Administration

Lead sponsor

National Cancer Institute (NCI)

Target enrolment

94 participants

Study type

INTERVENTIONAL

Phase

Phase 3

Status

Active, not recruiting

First posted

May 13, 2015

Last updated on the registry

Jul 31, 2026

Age

18 Years

Sex

ALL

Study contact

No public contact is listed on the official record.

Eligibility criteria

Reproduced verbatim from the official record. Eligibility is decided by the study team, never by this page.

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