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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: FCR and Ibrutinib; Drug: BR and Ibrutinib; Drug: Ibrutinib and Thalidomide

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zengjun Li; Phone Number: +86 13642138692; Email: lizengjun@ihcams.ac.cn
• Study Contact Backup: Name: Tingyu Wang; Phone Number: +86 15692201678; Email: wangtingyu@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 30020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
      • Contact: Zengjun Li; Phone Number: +86 13642138692; Email: lizengjun@ihcams.ac.cn
      • Contact: Tingyu Wang; Phone Number: +86 15692201678; Email: wangtingyu@ihcams.ac.cn
      • Sub-Investigator: Tingyu Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.; 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）；; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	Rate of complete remission	3 months after completion of induction therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	5 years
ORR	Overall Response Rate	3 months after completion of induction therapy
PFS	Progression-free survival	5 years
MRD negative rate	the rate of undetectable tumor cells in bone marrow and/or peripheral blood by multicolor flow cytometry	3 months after completion of induction therapy
DoR	Duration of Response	5 years
Treatment-related side effects		10 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Investigators: Principal Investigator: Zengjun Li, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Anticipated): December 15, 2022
• Study Completion (Anticipated): December 30, 2027

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: June 6, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: rituximab; Therapeutics; cyclophosphamide; Chronic Lymphocytic Leukemia; ibrutinib; fludarabine; treatment-naive; bendamustine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: IHBDH-IIT2018009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No