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A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive Patients With CLL (BDHCLL001)

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ClinicalTrials.gov Identifier: NCT03980002
Recruitment Status : Recruiting
First Posted : June 10, 2019
Last Update Posted : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
TingyuWang, Institute of Hematology & Blood Diseases Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: FCR and Ibrutinib Drug: BR and Ibrutinib Drug: Ibrutinib and Thalidomide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive Patients With Chronic Lymphocytic Leukemia
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : December 15, 2022
Estimated Study Completion Date : December 30, 2027


Arm Intervention/treatment
Experimental: FCR/BR alternating with ibrutinib
FCR/BR→ ibrutinib✖️3months→FCR/BR→ ibrutinib✖️3months→FCR/BR→Maintenance therapy
Drug: FCR and Ibrutinib

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

Drug: BR and Ibrutinib

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


Drug: Ibrutinib and Thalidomide

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.





Primary Outcome Measures :
  1. CRR [ Time Frame: 3 months after completion of induction therapy ]
    Rate of complete remission


Secondary Outcome Measures :
  1. ORR [ Time Frame: 3 months after completion of induction therapy ]
    Overall Response Rate

  2. OS [ Time Frame: 5 years ]
    Overall survival

  3. PFS [ Time Frame: 5 years ]
    Progression-free survival

  4. MRD negative rate [ Time Frame: 3 months after completion of induction therapy ]
    the rate of undetectable tumor cells in bone marrow and/or peripheral blood by multicolor flow cytometry

  5. DoR [ Time Frame: 5 years ]
    Duration of Response

  6. Treatment-related side effects [ Time Frame: 10 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03980002


Contacts
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Contact: Zengjun Li +86 13642138692 lizengjun@ihcams.ac.cn
Contact: Tingyu Wang +86 15692201678 wangtingyu@ihcams.ac.cn

Locations
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China, Tianjin
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Recruiting
Tianjin, Tianjin, China, 30020
Contact: Zengjun Li    +86 13642138692    lizengjun@ihcams.ac.cn   
Contact: Tingyu Wang    +86 15692201678    wangtingyu@ihcams.ac.cn   
Principal Investigator: Zengjun Li         
Sub-Investigator: Tingyu Wang         
Sponsors and Collaborators
Institute of Hematology & Blood Diseases Hospital
Investigators
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Principal Investigator: Zengjun Li Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

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Responsible Party: TingyuWang, Attending doctor, Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier: NCT03980002     History of Changes
Other Study ID Numbers: IHBDH-IIT2018009
First Posted: June 10, 2019    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by TingyuWang, Institute of Hematology & Blood Diseases Hospital:
Chronic Lymphocytic Leukemia
Therapeutics
ibrutinib
fludarabine
rituximab
bendamustine
cyclophosphamide
treatment-naive

Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Thalidomide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors