A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive Patients With CLL

Prior treatment

• Requirement for continuous anticoagulation drugs.
• Major surgery within 30 days(excluding lymph node biopsy).

Other illness

• History of malignant tumour except CLL in the past 1year(including active central nervous system (CNS) involvement with lymphoma).
• Have active autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, and require treatment.
• Severe or uncontrolled infection.
• Other serious medical diseases that may affect the study（eg. Uncontrolled diabetes, gastric ulcer, other severe cardiopulmonary disease),and final decided by the investigator.
• Ongoing and uncontrolled bleeding
• History of major life-threatening bleeding, especially due to irreversible cause.
• Allergy to any drug used in the study.

Lab values

• 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.

Age

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

Other

• Transformed to large cell lymphoma manifested by clinical evidence, or progressed to prolymphocytic leukemia(PLL).
• Central nervous system (CNS) dysfunction with clinical manifestation.

• Men or women ≥ 18 years and ≤ 75 of age.
• Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
• Treatment-naive patients. Those patients received short-term substandard treatment are permitted if meet all the items listed below:
  • Untreated with combined chemotherapy such as CHOP ,COP and so on.
  • Unteated with chemotherapy regimens including fludarabine and bendamustine.
  • Unteated with Ibrutinib.
  • If treated with chlorambucil or cyclophosphamide,should less than 3 weeks.
  • If treated with interferon, should less than 6 months.
  • No objective response are achieved (PR or CR).
• CLL/SLL requiring treatment as defined by at least one of the following criteria:
  • Development of, or worsening of, anemia to Hb\<100g/L (non-hemolytic) .
  • Development of, or worsening of, thrombocytopenia to PLT\<100,000/L.
  • Massive (≥ 6 cm below left costal margin), progressive or symptomatic splenomegaly.
  • Massive nodes (≥ 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy .
  • 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)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Expected to survival period for 3 months or more.