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Clinical Trial 18964

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT02443077

Phase: Phase III
Principal Investigator: Khimani, Farhad

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

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

Summary

The purpose of this study is to directly compare any good and bad effects of using an oral medication, ibrutinib, along with the AutoHCT versus AutoHCT alone.

Objective

Primary: To evaluate the ability of ibrutinib to improve 24-month progression free survival (PFS) compared to placebo. Secondary: To evaluate the ability of ibrutinib to improve overall survival (OS) compared to placebo. To evaluate the ability of ibrutinib to improve progression free survival (PFS) compared to placebo. To evaluate the ability of ibrutinib to improve post-transplant response rates compared to placebo. To evaluate time to hematopoietic recovery in the two arms. To evaluate the safety and tolerability of ibrutinib compared to placebo. To evaluate the incidence of secondary malignancies in the two arms. To evaluate immune reconstitution in the two arms.

Treatments

Therapies

Bone Marrow Transplant; Therapy (NOS)

Medications

748645 (Ibrutinib); Ibrutinib (Imbruvica); PCI-32765 (Ibrutinib); Placebo ()

Inclusion Criteria

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

Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma

Determination of activated B-cell-like (ABC) subtype by pre-registration central review

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 => Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x upper limit of normal (ULN)

Creatinine less than or equal to 2.0 mg/dL OR creatinine clearance (calculated clearance permitted) >= 40 mL/min

Prothrombin time (PT)/ international normalized ration (INR) less than 1.5 x ULN and partial thromboplastin time (PTT) (activated [a]PTT) less than 1.5 x ULN

Have progressed or refractory to prior anthracycline-containing chemotherapy

No more than 3 prior regimens for large cell component; 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

Must have chemosensitive disease as defined by at least a partial response to salvage therapy at latest assessment

No major surgery within 7 days prior to registration and no minor surgery within 3 days prior to registration (with the exception of intravenous access placement, e.g., Hickman or peripherally inserted central catheter [PICC])

Not pregnant or nursing; for women of childbearing potential (WOCBP), a negative serum pregnancy test must be obtained within 14 days prior to registration. WOCBP and men must use adequate contraception from study start to one month after last dose of protocol therapy.

Should not require chronic use of strong CYP3A inhibitors or strong CYP3A inducers

Should not require concurrent therapeutic doses of steroids 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: No prior history of acquired immunodeficiency syndrome (AIDS) defining conditions other than historically low CD4+ T-cell count or B-cell lymphoma; In opinion of 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 are not allowed; Patients with multi-drug resistant HIV are not eligible.

Eastern Cooperative Oncology Group (ECOG) performance status must be less than or equal to 2

Exclusion Criteria

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 less than or equal to 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)

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