Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This research study is evaluating a new drug called ibrutinib in combination with the
standard drugs fludarabine, cyclophosphamide, and rituximab (FCR) as a possible treatment for
Chronic Lymphocytic Leukemia (CLL).
Phase
Phase 2
Funding Agency/Sponsor
Externally Peer-Reviewed
Disease
Leukemia/heme
Enrollment Eligibility
Inclusion Criteria:
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic
lymphoma. as per IW-CLL 2008 criteria. Patients must also require therapy for that
diagnosis, based on meeting at least one of the following criteria:
- evidence of progressive marrow failure as manifested by the development of, or
worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x
10^9/L)
- massive (≥ 6 cm below the left costal margin), progressive, or symptomatic
splenomegaly
- massive nodes (at least 10 cm longest diameter), progressive, or symptomatic
lymphadenopathy
- progressive lymphocytosis with an increase of more than 50% over a 2-month period or
LDT of <6 months. Lymphocyte doubling time may be obtained by linear regression
extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an
observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts
of <30 x 10^9/L, LDT should not be used as a single parameter to define indication for
treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other
than CLL (eg, infections) should be excluded
- autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids
or other standard therapy
- documented constitutional symptoms, defined as 1 or more of the following
disease-related symptoms or signs:
- unintentional weight loss >10% within 6 months prior to screening
- significant fatigue (inability to work or perform usual activities)
- fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without
evidence of infection
- night sweats for more than 1 month prior to screening without evidence of
infection
- No prior CLL-directed therapy that was instituted due to patient previously
meeting IW-CLL 2008 criteria for treatment
- Age greater than or equal to 18 years and less than or equal to 65. Because
CLL is extremely rare in persons <18 years of age, children are excluded
from this study. Because iFCR is an aggressive therapy that is likely to be
less well-tolerated even in fit elderly subjects, persons > 65 years of age
are excluded
- ECOG performance status ≤ 1
- Adequate hematologic function independent of growth factor support for at
least 7 days prior to screening and randomization, with the exception of
pegylated G-CSF (pegfilgrastim) and darbepoetin which cannot be administered
within 14 days of screening.
- Patients must meet the following hematologic criteria at screening:
- Absolute neutrophil count ≥ 750 cells/mm3 (0.75 x 109/L).
- Platelet count ≥ 50,000 cells/mm3 (50 x 109/L).
- Hemoglobin ≥ 8 g/L - Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit
of normal (ULN)
- Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
non-hepatic origin)
- Adequate renal function defined by serum creatinine >1.5 x ULN
- PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN.
- The effects of ibrutinib on the developing human fetus are unknown. For this
reason and because similar agents are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation.
Exclusion Criteria:
- Concurrent Conditions:
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present
for ≥ 3 years before the first dose of study drug and felt to be at low risk for
recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.,
or chronic administration of >20 mg/day of prednisone) within 28 days of the first
dose of study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤ 14 days before the
first dose of study drug.
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
(HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core
antibody or hepatitis B surface antigen must have a negative polymerase chain reaction
(PCR) result before enrollment. Those who are PCR positive will be excluded.
- Any uncontrolled active systemic infection.
- Major surgery within 4 weeks of first dose of study drug.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in
the investigator's opinion, could compromise the subject's safety or put the study
outcomes at undue risk.
- Currently active, clinically significant cardiovascular disease, such as uncontrolled
arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
Association Functional Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to randomization.
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel, symptomatic
inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
obstruction.
- Lactating or pregnant.
- Patients receiving any other study agents
- Patients with known CNS involvement
- Baseline QTcF >480 ms. NOTE: This criterion does not apply to patients with a left
bundle branch block.
- Patients who require warfarin or other vitamin K antagonists for anticoagulation
(other anticoagulants are allowed after consultation with the Principal Investigator).
- Concurrent administration of medications or foods that are strong inhibitors or
inducers of CYP3A
- Patients with ongoing use of prophylactic antibiotics are eligible as long as there is
no evidence of active infection and the antibiotic is not included on the list of
prohibited medications
- Significant co-morbid condition or disease which in the judgment of the Principal
Investigator would place the patient at undue risk or interfere with the study
- Unable to receive prophylactic treatment for pneumocystis
- Patients with del(17p) confirmed by FISH in ≥20% of cells or on stimulated
karyotype3.2.24 Patients with del(17p) confirmed by FISH in ≥20% of cells or on
stimulated karyotype
- Patients with unmutated IGHV who also have a complex karyotype on a stimulated
karyotype