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

NCT03980002 | Recruiting Phase 2

• 1 other identifier: IHBDH-IIT2018009
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Therapeutics; ibrutinib; fludarabine; rituximab; bendamustine; cyclophosphamide; treatment-naive

Outcome Measures

Primary Outcomes (1)

• CRR

  Rate of complete remission

  3 months after completion of induction therapy

Secondary Outcomes (6)

• ORR

  3 months after completion of induction therapy

• OS

  5 years

• PFS

  5 years

• MRD negative rate

  3 months after completion of induction therapy

• DoR

  5 years

Study Arms (1)

FCR/BR alternating with ibrutinib

EXPERIMENTAL

FCR/BR→ ibrutinib✖️3months→FCR/BR→ ibrutinib✖️3months→FCR/BR→Maintenance therapy

Drug: FCR and Ibrutinib; Drug: BR and Ibrutinib; Drug: Ibrutinib and Thalidomide

Interventions

FCR and Ibrutinib DRUG

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

FCR/BR alternating with ibrutinib

BR and Ibrutinib DRUG

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

FCR/BR alternating with ibrutinib

Ibrutinib and Thalidomide DRUG

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.

FCR/BR alternating with ibrutinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, Tianjin Municipality, 30020, China

RECRUITING

Related Publications (1)

• Wang T, Yan Y, Wang H, Sun Y, Liu X, Lyu R, Xiong W, An G, Liu W, Xu Y, Deng S, Wang Q, Du C, Huang L, Zou D, Zhao Y, Qiu L, Li Z, Yi S. Ibrutinib alternating with three cycles of interval fludarabine, cyclophosphamide, and rituximab (FCR) in adults with untreated chronic lymphocytic leukaemia as time-limited regimen: a single-arm, multicentre phase 2 trial in China. EClinicalMedicine. 2025 Dec 5;90:103688. doi: 10.1016/j.eclinm.2025.103688. eCollection 2025 Dec.

  PMID: 41497516 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Receptors, Fc; ibrutinib; Thalidomide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Zengjun Li

  Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zengjun Li

CONTACT

+86 13642138692; lizengjun@ihcams.ac.cn

Tingyu Wang

CONTACT

+86 15692201678; wangtingyu@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending doctor

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 10, 2019
• Study Start: May 15, 2019
• Primary Completion: December 15, 2022
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)