A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive Patients With CLL
A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive Patients With CLL
This is a prospective multicenter phase 2 study designed with the purpose to evaluate the
 response rate and safety of treatment with FCR/BR alternating with ibrutinib in
 treatment-naive patients with chronic lymphocytic leukemia.
Inclusion Criteria:

 1. Men or women ≥ 18 years and ≤ 75 of age.

 2. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.

 3. Treatment-naive patients. Those patients received short-term substandard treatment are
 permitted if meet all the items listed below:

 1. Untreated with combined chemotherapy such as CHOP ,COP and so on.

 2. Unteated with chemotherapy regimens including fludarabine and bendamustine.

 3. Unteated with Ibrutinib.

 4. If treated with chlorambucil or cyclophosphamide,should less than 3 weeks.

 5. If treated with interferon, should less than 6 months.

 6. No objective response are achieved (PR or CR).

 4. CLL/SLL requiring treatment as defined by at least one of the following criteria:

 1. Development of, or worsening of, anemia to Hb<100g/L (non-hemolytic) .

 2. Development of, or worsening of, thrombocytopenia to PLT<100,000/L.

 3. Massive (≥ 6 cm below left costal margin), progressive or symptomatic
 splenomegaly.

 4. Massive nodes (≥ 10 cm in longest diameter), or progressive or symptomatic
 lymphadenopathy .

 5. Progressive lymphocytosis with an increase of > 50% over a 2-month period or
 lymphocyte-doubling time 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 patients
 with initial blood lymphocyte counts of < 30,000/L, LDT should not be used as a
 single parameter to define treatment indication. In addition, factors
 contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (eg,
 infection, use glucocorticoid) should be excluded. f)Symptomatic or functional
 extranodal sites involved s (eg. Skin,kidney, lungs and so on).

 g)Constitutional symptoms, defined as any 1 or more of the following disease-related
 symptoms or signs: i. Unintentional weight loss of ≥ 10% within the previous 6 months
 ii.Significant fatigue (ie, inability to work or perform usual activities)

 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

 6. Expected to survival period for 3 months or more.

 Exclusion Criteria:

 1. History of malignant tumour except CLL in the past 1year(including active central
 nervous system (CNS) involvement with lymphoma).

 2. Transformed to large cell lymphoma manifested by clinical evidence, or progressed to
 prolymphocytic leukemia(PLL).

 3. Have active autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, and
 require treatment.

 4. Inadequate hepatic and renal function defined as: AST and ALT >4.0 x upper limit of
 normal (ULN), bilirubin >2.0 x upper limit of normal (ULN), Adequate renal function
 defined by serum creatinine >1.5 x upper limit of normal (ULN),unrelated to lymphoma.

 5. Severe or uncontrolled infection.

 6. Central nervous system (CNS) dysfunction with clinical manifestation.

 7. Other serious medical diseases that may affect the study（eg. Uncontrolled diabetes,
 gastric ulcer, other severe cardiopulmonary disease),and final decided by the
 investigator.

 8. Ongoing and uncontrolled bleeding

 9. History of major life-threatening bleeding, especially due to irreversible cause.

 10. Requirement for continuous anticoagulation drugs.

 11. Major surgery within 30 days(excluding lymph node biopsy).

 12. Pregnant or Lactating women, or women of reproductive age refusal to take
 contraceptive measures.

 13. Allergy to any drug used in the study.