Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical 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). 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.
Phase
Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Lymphoma
Enrollment Eligibility
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