Chronic Lymphocytic LeukemiaPhase 2iFCRNCT02251548
A Phase II Study of Ibrutinib Plus FCR in Previously Untreated, Younger Patients With Chronic Lymphocytic Leukemia
A Phase 2 study testing Ibrutinib, Fludarabine and Cyclophosphamide in people with Chronic Lymphocytic Leukemia and Leukemia, run by Dana-Farber Cancer Institute at 9 sites in United States.
Trial summary
This research study is evaluating a new drug called ibrutinib in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR) as a possible treatment for Chronic Lymphocytic Leukemia (CLL). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Leukemia
- What is being tested?
- Ibrutinib, Fludarabine and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 9 sitesUnited States
- Study dates
- Oct 2014to Jan 2027
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma. as per IW-CLL 2008 criteria. Patients must also require therapy for that diagnosis, based on meeting at least one of the following criteria:
- evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 10^9/L)
- massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
- massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
- progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT 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 subjects with initial blood lymphocyte counts of <30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded
- autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
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- documented constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:
- unintentional weight loss >10% within 6 months prior to screening
- significant fatigue (inability to work or perform usual activities)
- fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection
- night sweats for more than 1 month prior to screening without evidence of infection
- No prior CLL-directed therapy that was instituted due to patient previously meeting IW-CLL 2008 criteria for treatment
- Age greater than or equal to 18 years and less than or equal to 65. Because CLL is extremely rare in persons <18 years of age, children are excluded from this study. Because iFCR is an aggressive therapy that is likely to be less well-tolerated even in fit elderly subjects, persons > 65 years of age are excluded
- ECOG performance status ≤ 1
- Adequate hematologic function independent of growth factor support for at least 7 days prior to screening and randomization, with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which cannot be administered within 14 days of screening.
- Patients must meet the following hematologic criteria at screening:
- Absolute neutrophil count ≥ 750 cells/mm3 (0.75 x 109/L).
- Platelet count ≥ 50,000 cells/mm3 (50 x 109/L).
- Hemoglobin ≥ 8 g/L - Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN)
- Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Adequate renal function defined by serum creatinine >1.5 x ULN
- PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN.
- The effects of ibrutinib on the developing human fetus are unknown. For this reason and because similar agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
Who cannot join
- Concurrent Conditions:
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone) within 28 days of the first dose of study drug.
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- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug.
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
- Any uncontrolled active systemic infection.
- Major surgery within 4 weeks of first dose of study drug.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Lactating or pregnant.
- Patients receiving any other study agents
- Patients with known CNS involvement
- Baseline QTcF >480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block.
- Patients who require warfarin or other vitamin K antagonists for anticoagulation (other anticoagulants are allowed after consultation with the Principal Investigator).
- Concurrent administration of medications or foods that are strong inhibitors or inducers of CYP3A
- Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not included on the list of prohibited medications
- Significant co-morbid condition or disease which in the judgment of the Principal Investigator would place the patient at undue risk or interfere with the study
- Unable to receive prophylactic treatment for pneumocystis
- Patients with del(17p) confirmed by FISH in ≥20% of cells or on stimulated karyotype3.2.24 Patients with del(17p) confirmed by FISH in ≥20% of cells or on stimulated karyotype
- Patients with unmutated IGHV who also have a complex karyotype on a stimulated karyotype
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Miami Sylvester Comprehensive Cancer Center
Coral Gables, Florida, 33146
University of Miami Sylvester Comprehensive Cancer Center
Deerfield Beach, Florida, 33442
Duke University Medical Center
Durham, North Carolina, 27710
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Unversity of Miami Sylvester Comprehensve Cancer Center
Miami, Florida, 33136
University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase II Study of Ibrutinib in Combination With Fludarabine, Cyclophosphamide, and Rituximab (iFCR) in Previously Untreated, Younger Patients With Chronic Lymphocytic Leukemia
This research study is evaluating a new drug called ibrutinib in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR) as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Read the detailed description
Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a protein called Bruton's tyrosine kinase (BTK) that helps CLL cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing. Ibrutinib has been FDA approved for the treatment of CLL patients who have received at least one prior treatment; however, the FDA has not yet approved ibrutinib as the first treatment for previously untreated CLL. Therefore, ibrutinib is still considered to be study drug, which means it is still being studied.
Fludarabine, cyclophosphamide, and rituximab (FCR) are intravenous chemotherapy and antibody drugs that together are a standard chemotherapy regimen used for younger patients with CLL. Although FCR is highly effective, it does not typically lead to cure.
In this research study, the investigators are combining a new treatment for CLL, ibrutinib, with a standard chemotherapy regimen for CLL, FCR, to determine whether this combination (iFCR) is safe and effective for patients with previously untreated CLL.
- Conditions
- Chronic Lymphocytic Leukemia, Leukemia
- Being tested
- Ibrutinib, Fludarabine, Cyclophosphamide, Rituximab
- Keywords
- Chronic lymphocytic leukemia, Leukemia
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica™
Oral BTK inhibitor
FludarabineDrug
Also called Fludara
IV purine analogue chemotherapy agent
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
IV alkylator chemotherapy agent
RituximabDrug
Also called Rituxan®
IV anti-CD20 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib | Experimental | - Ibrutinib-
* Oral, daily during each cycle
* fludarabine-administered at standard dosing for up to 6 cycles
* cyclophosphamide-administered at standard dosing for up to 6 cycles
* rituximab-administered at standard dosing for up to 6 cycles Receives: Drug: Ibrutinib; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part I: Participants Who Achieve a Minimal Residual Disease (MRD) Negative Complete Response (CR) in the Bone Marrow at 2 Months Post FCR
To assess the number of participants who achieve an MRD negative complete response at the 2 months post last dose of FCR timepoint by 2008 IW-CLL criteria ( Hallek et. al). Participants will have a bone marrow biopsy procedure 2 months after completing combination therapy (Ibrutinib+ FCR) in tandem with a chest, neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4.
Measured: 2 months after completing combination therapy
Secondary outcomes (11)
Overall Response Rate
The objective response rate (ORR) was defined as the proportion of participants achieving CR+CRi+PR, Complete Response with incomplete count recovery (CRi) or partial response (PR) based on 2008 IW-CLL criteria criteria (Hallek et al., 2008).
Measured: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Complete Response Rate (CRR)
CRR defined as the proportion of participants achieving complete response. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008).
Measured: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Partial Response Rate (PRR)
PRR defined as the proportion of participants achieving partial response. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008).
Measured: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Median Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.
Measured: Disease will be evaluated through imaging cycle 3-6 day 1, and In long-term follow-up, after removal or until participant withdrawal, death, or removal from study. Median follow-up is: 63.24 months (range: 6.83-95.8).
Median Overall Survival (OS)
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: Median follow-up is: 63.24 months (range: 6.83-95.8).
Rate of MRD Negative CR After 3 Cycles of iFCR
To determine the rate of minimal residual disease negative complete response (MRD negative CR) in the bone marrow after 3 cycles of ibrutinib + FCR. Participants will have a bone marrow biopsy procedure after completing 3 cycles in tandem with a chest, neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Measured: After 3 cycles of iFCR for each patient completing 3 cycles
1-year Combined Response With MRD From Bone Marrow
Combined response with MRD from bone marrow reported as the MRD-negative CR. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Measured: at 1 year
Number of Participants Who Convert From Bone Marrow MRD Negative PR to Bone Marrow MRD Negative CR After 1 Year of Ibrutinib Maintenance
To determine the rate of minimal residual disease negative complete response (MRD negative CR) in the bone marrow at 12 months from start of therapy, participants will have a bone marrow biopsy procedure at the 1 year timepoint after completing combination therapy (ibrutinib + FCR) in tandem with a chest, neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Measured: 12 months ( 1year) after starting therapy
Number of Participants Who Convert From Bone Marrow MRD Negative PR to Bone Marrow MRD Negative CR After 2 Years on Treatment
MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)- Bone marrow biopsies will be performed at baseline, after cycle 3, 2 months post FCR, at 1 year and 2 years of ibrutinib maintenance, and as clinically indicated thereafter- Participants will have a bone marrow biopsy procedure 24 months after completing combination therapy (Ibrutinib+ FCR) in tandem with a chest, neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4.
Measured: 2 years (24 months) from start of therapy
Median Time to Bone Marrow MRD Negativity
MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)-
Measured: Bone marrow biopsies will be performed at baseline, after cycle 3, 2 months post FCR, at 1 year and 2 years of ibrutinib maintenance, and as clinically indicated thereafter
Participants Who Convert From Bone Marrow MRD Negativity to MRD Positivity in Participants Who Discontinue Ibrutinib
.MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Measured: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2014 (estimated)
- Study startOct 2014
- Primary completionJan 2025
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC., The Leukemia and Lymphoma Society, Blood Cancer Research Partnership
- Responsible party
- Principal investigator, Matthew S. Davids, MD, Dana-Farber Cancer Institute
- Investigators
- Matthew Davids, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02251548
- Sponsor's protocol ID
- 14-296
- Acronym
- iFCR
- Status last verified
- Jun 2026
- First submitted
- 23 Sep 2014
- Last updated
- 21 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ahn IE, Brander DM, Ren Y, Zhou Y, Tyekucheva S, Walker HA, Black R, Montegaard J, Alencar A, Shune L, Omaira M, Jacobson CA, Armand P, Ng SY, Crombie J, Fisher DC, LaCasce AS, Arnason J, Hochberg EP, Takvorian RW, Abramson JS, Brown JR, Davids MS. Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL. Blood Adv. 2024 Feb 27;8(4):832-841. doi: 10.1182/bloodadvances.2023011574.
PubMed 38163317Davids MS, Brander DM, Kim HT, Tyekucheva S, Bsat J, Savell A, Hellman JM, Bazemore J, Francoeur K, Alencar A, Shune L, Omaira M, Jacobson CA, Armand P, Ng S, Crombie J, LaCasce AS, Arnason J, Hochberg EP, Takvorian RW, Abramson JS, Fisher DC, Brown JR; Blood Cancer Research Partnership of the Leukemia & Lymphoma Society. Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2019 Aug;6(8):e419-e428. doi: 10.1016/S2352-3026(19)30104-8. Epub 2019 Jun 14.
PubMed 31208944
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Ibrutinib in Combination With Fludarabine, Cyclophosphamide, and Rituximab (iFCR) in Previously Untreated, Younger Patients With Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT02251548
- Acronym / sponsor ID
- iFCR / 14-296
- Conditions
- Chronic Lymphocytic Leukemia, Leukemia
- Keywords
- Chronic lymphocytic leukemia, Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC., The Leukemia and Lymphoma Society, Blood Cancer Research Partnership
- Study start
- Oct 2014 (actual)
- Primary completion
- Jan 2025 (actual)
- Study completion
- Jan 2027 (estimated)
- First posted
- 29 Sep 2014 (estimated)
- Results
- Posted 15 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is evaluating a new drug called ibrutinib in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR) as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Detailed description
Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a protein called Bruton's tyrosine kinase (BTK) that helps CLL cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing. Ibrutinib has been FDA approved for the treatment of CLL patients who have received at least one prior treatment; however, the FDA has not yet approved ibrutinib as the first treatment for previously untreated CLL. Therefore, ibrutinib is still considered to be study drug, which means it is still being studied.
Fludarabine, cyclophosphamide, and rituximab (FCR) are intravenous chemotherapy and antibody drugs that together are a standard chemotherapy regimen used for younger patients with CLL. Although FCR is highly effective, it does not typically lead to cure.
In this research study, the investigators are combining a new treatment for CLL, ibrutinib, with a standard chemotherapy regimen for CLL, FCR, to determine whether this combination (iFCR) is safe and effective for patients with previously untreated CLL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib | Experimental | Drug: Ibrutinib, Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Rituximab- Ibrutinib- * Oral, daily during each cycle * fludarabine-administered at standard dosing for up to 6 cycles * cyclophosphamide-administered at standard dosing for up to 6 cycles * rituximab-administered at standard dosing for up to 6 cycles |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma. as per IW-CLL 2008 criteria. Patients must also require therapy for that diagnosis, based on meeting at least one of the following criteria:
- evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 10^9/L)
- massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
- massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
- progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT 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 subjects with initial blood lymphocyte counts of <30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded
Key exclusion criteria (27 listed)
- Concurrent Conditions:
- History of other malignancies, except:
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone) within 28 days of the first dose of study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: Imbruvica™Oral BTK inhibitor | Drug | Ibrutinib |
| FludarabineAlso: FludaraIV purine analogue chemotherapy agent | Drug | Ibrutinib |
| CyclophosphamideAlso: Cytoxan®, Neosar®IV alkylator chemotherapy agent | Drug | Ibrutinib |
| RituximabAlso: Rituxan®IV anti-CD20 monoclonal antibody | Drug | Ibrutinib |
Primary outcome
Part I: Participants Who Achieve a Minimal Residual Disease (MRD) Negative Complete Response (CR) in the Bone Marrow at 2 Months Post FCR
Time frame: 2 months after completing combination therapy
To assess the number of participants who achieve an MRD negative complete response at the 2 months post last dose of FCR timepoint by 2008 IW-CLL criteria ( Hallek et. al). Participants will have a bone marrow biopsy procedure 2 months after completing combination therapy (Ibrutinib+ FCR) in tandem with a chest, neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4.
11 secondary outcomes
Overall Response Rate
Time frame: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Complete Response Rate (CRR)
Time frame: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Partial Response Rate (PRR)
Time frame: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Median Progression-Free Survival (PFS)
Time frame: Disease will be evaluated through imaging cycle 3-6 day 1, and In long-term follow-up, after removal or until participant withdrawal, death, or removal from study. Median follow-up is: 63.24 months (range: 6.83-95.8).
Median Overall Survival (OS)
Time frame: Median follow-up is: 63.24 months (range: 6.83-95.8).
Rate of MRD Negative CR After 3 Cycles of iFCR
Time frame: After 3 cycles of iFCR for each patient completing 3 cycles
1-year Combined Response With MRD From Bone Marrow
Time frame: at 1 year
Number of Participants Who Convert From Bone Marrow MRD Negative PR to Bone Marrow MRD Negative CR After 1 Year of Ibrutinib Maintenance
Time frame: 12 months ( 1year) after starting therapy
Number of Participants Who Convert From Bone Marrow MRD Negative PR to Bone Marrow MRD Negative CR After 2 Years on Treatment
Time frame: 2 years (24 months) from start of therapy
Median Time to Bone Marrow MRD Negativity
Time frame: Bone marrow biopsies will be performed at baseline, after cycle 3, 2 months post FCR, at 1 year and 2 years of ibrutinib maintenance, and as clinically indicated thereafter
Participants Who Convert From Bone Marrow MRD Negativity to MRD Positivity in Participants Who Discontinue Ibrutinib
Time frame: Response evaluated at 2 months post iFCR. Treatment up to 6 cycles (28 days each).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38163317Ahn IE, Brander DM, Ren Y, Zhou Y, Tyekucheva S, Walker HA, Black R, Montegaard J, Alencar A, Shune L, Omaira M, Jacobson CA, Armand P, Ng SY, Crombie J, Fisher DC, LaCasce AS, Arnason J, Hochberg EP, Takvorian RW, Abramson JS, Brown JR, Davids MS. Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL. Blood Adv. 2024 Feb 27;8(4):832-841. doi: 10.1182/bloodadvances.2023011574.
- Derived from this study: PubMed 31208944Davids MS, Brander DM, Kim HT, Tyekucheva S, Bsat J, Savell A, Hellman JM, Bazemore J, Francoeur K, Alencar A, Shune L, Omaira M, Jacobson CA, Armand P, Ng S, Crombie J, LaCasce AS, Arnason J, Hochberg EP, Takvorian RW, Abramson JS, Fisher DC, Brown JR; Blood Cancer Research Partnership of the Leukemia & Lymphoma Society. Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2019 Aug;6(8):e419-e428. doi: 10.1016/S2352-3026(19)30104-8. Epub 2019 Jun 14.
- Individual participant dataSharing planned: No
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RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Davids, MD principal investigator
Dana-Farber Cancer Institute
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib, Fludarabine and Cyclophosphamide in people with Chronic Lymphocytic Leukemia and Leukemia, run by Dana-Farber Cancer Institute at 9 sites 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 24 inclusion and 27 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 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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 15 May 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?
Part I: Participants Who Achieve a Minimal Residual Disease (MRD) Negative Complete Response (CR) in the Bone Marrow at 2 Months Post FCR (time frame: 2 months after completing combination therapy). 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 NCT02251548, which also lists 2 linked publications.
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 21 Jul 2026.