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.

Key Inclusion Criteria:

• Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
• Determination of activated B-cell-like (ABC) subtype by pre-registration central pathology review
• Patient must have progressed or be refractory to prior anthracycline-containing chemotherapy (e.g. rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP], dose adjusted doxorubicin hydrochloride, etoposide phosphate, vincristine sulfate, cyclophosphamide, prednisone [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 site radiotherapy do not count as lines 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 treatment and no minor surgery =< 3 days prior to treatment (with the exception of intravenous access placement, e.g. Hickman or peripherally inserted central catheter [PICC])
• Human immunodeficiency virus (HIV) infected patients are eligible provided they meet all other eligibility criteria, and:
◦There is no prior history of acquired immune deficiency syndrome (AIDS) defining conditions other than historically low cluster of differentiation (CD)4+ 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 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 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

Phase III
Alison Conlin, M.D.
Laurie Delanty

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.