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 Chronic Lymphocytic Leukemia
Institute of Hematology & Blood Diseases Hospital, China
50 participants
May 15, 2019
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria18
- 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.
Exclusion Criteria13
- History of malignant tumour except CLL in the past 1year(including active central nervous system (CNS) involvement with lymphoma).
- Transformed to large cell lymphoma manifested by clinical evidence, or progressed to prolymphocytic leukemia(PLL).
- Have active autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, and require treatment.
- 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.
- Severe or uncontrolled infection.
- Central nervous system (CNS) dysfunction with clinical manifestation.
- 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.
- Requirement for continuous anticoagulation drugs.
- Major surgery within 30 days(excluding lymph node biopsy).
- Pregnant or Lactating women, or women of reproductive age refusal to take contraceptive measures.
- Allergy to any drug used in the study.
Interventions
Induction treatment: Patients \<65 y and without significant comorbidities are given FCR 1or 2 courses (If patients' white blood cell count \<10×10\^9/L after first course, the second course can be saved). Then, patients takes ibrutinib orally for 3 months alternating with FCR in 2 cylcles. 1. FCR： F（Fludarabine）：25mg/m2·d，d1-3； C（Cyclophosphamide）：CTX 250mg /m2·d，d1-3； R（Rituximab）：375mg/m2 d0（first course），500mg/m2 d0（subsequent courses）； 2. Ibrutinib:420mg/d
Induction treatment: Patients ≥65y and ≤75 y or \<65 y but with comorbidities, are given BR 1or 2 courses (If patients' white blood cell count drop to below10×10\^9/Lafter first course, the second course can be saved). Then, patients takes ibrutinib orally for 3 months alternating with BR in 2 cylcles. 1.BR： B（Bendamustine）：90mg/m2·d，d1-2； R（Rituximab）：375mg/m2 d0（first course），500mg/m2 d0（subsequent courses）； 2. Ibrutinib: 420mg/d
Maintenance treatment: After induction treatment, recommend ( but not mandatory) Ibrutinib or thalidomide monotherapy(according to patients preferrance) for MRD-positive patients.For MRD-negative patients, recommend ( but not mandatory) no maintenance therapy.
Locations(1)
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NCT03980002