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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

ELIGIBILITY CRITERIA (STEP 1)

  • Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, high grade B-cell lymphoma not otherwise specified, 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 for hemoglobin).
  • Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted (corrected for hemoglobin).
  • Forced vital capacity (FVC) ≥ 40% of predicted (corrected for hemoglobin).
  • 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., R-CHOP, 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 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; 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.
  • 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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Patrick Johnston, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20314851

Mayo Clinic Footer