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Chronic Lymphocytic LeukemiaPhase 2NCT02514083

A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL

A Phase 2 study testing Ibrutinib and Fludarabine in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given in cycles 3 and 4. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
9 Dec 2015to 23 Oct 2034
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • 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
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  • 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
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
  • Absolute neutrophil count (ANC) > 750/microL, platelets > 50,000/microL
  • 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.
  • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
  • 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)

Who cannot join

  • 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, aspartate aminotransferase (AST) or alanine transaminase (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 glomerular filtration rate (GFR) < 30ml/min/1.73m(2) based on CKD-EPI
  • Life-threatening illness, medical condition or organ system dysfunction which, in the investigators 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: 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 is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patients. 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 or 24 weeks. The primary safety endpoint is the rate of treatment discontinuation after 6 cycles or 24 weeks.

Read the detailed description

Chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) are tumors of B cells that often affect elderly patients. While the cause of CLL is still unclear, studies have indicated critical factors required for the tumor cells. First, CLL cells grow and survive because they receive signals through the B-cell receptor (BCR); and second, CLL cells benefit from interactions with other cells, especially T cells.

The stimulation through the BCR can be reduced with ibrutinib, which is an oral drug that selectively inhibits Bruton's tyrosine kinase (BTK). In clinical trials, ibrutinib demonstrated safety and high response rates in patients with high-risk disease. Ibrutinib has gained FDA approval as a treatment for CLL patients with 17p deletion and for those who had at least one prior therapy. However, single-agent ibrutinib has limitations; the drug does not eliminate all the tumor cells, and, with time, the tumor cells may become resistant. Therefore, a combination of ibrutinib with other drugs could be beneficial. Here we chose fludarabine because it is a well-tolerated drug that has been used widely to treat CLL. Also, fludarabine can kill both malignant B cells and T cells that support the growth of leukemia cells. With this approach, we hope to restore a healthier immune system.

This study will investigate the safety and efficacy of ibrutinib combined with fludarabine. This protocol is intended for previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given only in cycles 3 and 4.

Being tested
Ibrutinib, Fludarabine
Keywords
Bruton's tyrosine kinase inhibitor, Fludarabine, Immune modulation
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called Imbruvica

    Ibrutinib 420mg PO daily for the duration of the study.

  • FludarabineDrug

    Also called Fludara

    Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Study groups in NCT02514083
Study groupRoleWhat they receive
Ibrutinib and short-course fludarabineExperimental* Ibrutinib 420 mg PO daily for the duration of the study * Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4
Receives: Drug: Ibrutinib; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Complete Response at 24 Weeks

    Rate of complete response at 24 weeks or after 6 cycles. Response assessment was conducted according to the guidelines from the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL).

    Measured: 24 weeks

  2. Rate of Treatment Discontinuation Within the First 24 Weeks

    Rate of treatment discontinuation within the first 24 weeks or 6 cycles due to intolerable side effects from study therapy

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2015 (estimated)
  2. Study start9 Dec 2015
  3. Primary completion2 Oct 2019
  4. Study completion23 Oct 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02514083
Sponsor's protocol ID
150172
Other IDs
15-H-0172
Status last verified
Mar 2026
First submitted
31 Jul 2015
Last updated
14 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016 Oct 13;128(15):1940-1943. doi: 10.1182/blood-2016-06-722991. Epub 2016 Aug 8.

    PubMed 27503501

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Fludarabine in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Complete Response at 24 Weeks (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02514083, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.

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