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

Has met at least one of the following indications for treatment: Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L) Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly One or more of the following disease-related symptoms: Weight loss >= 10% within the previous 6 months Grade 2 or 3 fatigue attributed to CLL Fevers > 100.5 Fahrenheit (F) for 2 weeks without evidence of infection Clinically significant night sweats without evidence of infection Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months

ECOG performance status between 0-2

Life expectancy of >= 12 months

Ability to tolerate FCR based therapy

Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault formula (obtained =< 14 days prior to registration)

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

Allergy and Immunology

Hematology

Oncology (Adult)

Sponsors

National Cancer Institute (NCI)