Official Title

A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

Purpose

This phase III trial studies ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. It is not yet known whether fludarabine phosphate, cyclophosphamide, and rituximab may work better than ibrutinib and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description

Eligibility Criteria

Inclusion Criteria

Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria

this includes previous documentation of: Biopsy-proven small lymphocytic lymphoma or Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following: Peripheral blood lymphocyte count of greater than 5 x 10^9/L Immunophenotype consistent with CLL defined as: The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc) Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression) Negative FISH analysis for t(11

14)(immunoglobulin heavy locus [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)

ECOG performance status between 0-2

Life expectancy of >= 12 months

Ability to tolerate FCR based therapy

Exclusion Criteria

No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLL

No deletion of 17p13 on cytogenetic analysis by FISH

No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment

patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation

No current use of corticosteroids

EXCEPTION: low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted

No previous use of corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL

prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed

Keywords and/or Specific Medical Conditions

Hematology

Oncology (Adult)

Sponsors

National Cancer Institute (NCI)