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Protocol Details

A Pilot Phase II Study Using Ibrutinib and Short-Course Fludarabine in Previously Untreated Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Tumors of B cells;
Hematopoietic Neoplasms;
Bruton's Tyrosine Kinase

Recruitment Keyword(s)



Hematopoietic Neoplasms;
Tumors of B Cells;
B-cell surface antigens CD19, CD20 and CD23;
T-cell antigen CD5;
B-cell receptor (BCR)

Investigational Drug(s)


Investigational Device(s)



Drug: Ibrutinib 420mg PO daily for the duration of the study.
Drug: Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Supporting Site

National Heart, Lung, and Blood Institute

This is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patiaents. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given in cycles 3 and 4. The primary efficacy endpoint is the rate of complete response after 6 cycles of 24 weeks. The primary safaety endpoint is the rate of treatment discontinuation after 6 cycles of 24 weeks.

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1. Men and women with histologically confirmed disease as defined by the following:

-CLL: clonal B-lymphocytosis greater than or equal to 5,000 cells/microL .

-SLL: lymphadenopathy with the tissue morphology of CLL but that are not leukemic, < 5,000 cells/microL.

-Immunophenotypic profile or immunohistochemistry read by an expert pathologist as consistent with CLL. This will include CD5, CD19, and CD20 expression by the CLL cells typically also with CD23 expression, but CD23 negative cases may be included if there is an absence of t(11;14).

2. Active disease as defined by at least one of the following (IWCLL consensus criteria):

-Weight loss greater than or equal to 10% within the previous 6 months

-Extreme fatigue

-Fevers of greater than 100.5 F for greater than or equal to 2 weeks without evidence of infection

-Night sweats for more than one month without evidence of infection

-Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

-Massive or progressive splenomegaly

-Massive nodes or clusters or progressive lymphadenopathy

-Progressive lymphocytosis with an increase of >50% over a 2-month period, or an anticipated doubling time of less than 6 months

3. Treatment naive CLL/SLL patients

-Treatment-naive CLL indicates no prior anti-CLL therapy. Anti-CLL therapy includes chemotherapies, monoclonal antibodies, and targeted agents with known or reasonably expected anti-leukemic activity.

4. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2

5. ANC > 750/microL, platelets > 50,000/microL

6. Agreement to use acceptable methods of contraception during the study and for 90 days after the last dose of study drug if sexually active and able to bear or beget children.

--Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.

--Male and female subjects who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices, complete abstinence, or sterilized partner) and a barrier method (e.g. condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug

7. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)


-Transformed CLL, including Hodgkin and non-Hodgkin lymphoma

- Active autoimmune hemolytic anemia or thrombocytopenia

- Known bleeding disorders

- Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless due to Gilbert s disease, AST/ ALT greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of liver, Child-Pugh class B or C

- Impaired renal function: estimated GFR < 30ml/min/1.73m(2) based on CKD-EPI

- Life-threatening illness, medical condition or organ system dysfunction which, in the investigator s opinion, could compromise the subject s safety, interfere with the absorption or metabolism of ibrutinib and fludarabine, or put the study outcomes at undue risk

-Concomitant immunomodulatory therapy, chemotherapy, radiotherapy or experimental therapy

- Active Hepatitis B or Hepatitis C infection

- HIV infection

- Female patients who are currently in pregnancy, or unwilling to use acceptable methods of contraception or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol.

- Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements.

- Unable to understand the investigational nature of the study or give informed consent.

- Individuals < 18 years old

- Known hypersensitivity to any component of ibrutinib or fludarabine

- Requires concomitant anticoagulation with Coumadin (warfarin) or other vitamin K antagonists.

- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for greater than or equal to 2 years or which will not limit survival to < 2 years

- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction

- History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug

- Major surgery within 4 weeks of first dose of study drug

- Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification, or a history of myocardial infarction or unstable angina, or acute coronary syndrome within 6 months of screening.

- Subjects who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitor.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Adrian U. Wiestner, M.D.
National Heart, Lung and Blood Institute (NHLBI)
NIHBC 10 - CRC BG RM 3-5140
(301) 594-6855

Susan Soto, R.N.
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room 4-5362
10 Center Drive
Bethesda, Maryland 20892
(301) 402-0797

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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