Prolymphocytic LeukemiaPhase 2NCT02007044
Ibrutinib With or Without Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
A Phase 2 study testing Ibrutinib, Quality-of-Life Assessment and Questionnaire Administration in people with Prolymphocytic Leukemia and Recurrent Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma
- What is being tested?
- Ibrutinib, Quality-of-Life Assessment and Questionnaire Administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2013to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Patients must have a diagnosis of CLL/small lymphocytic lymphoma (SLL) or prolymphocytic leukemia (PLL) and be previously treated; given the poor outcome of CLL/SLL/PLL patients with 17p deletion (del) or tumor protein (TP)53 mutation to standard frontline chemo-immunotherapy, such patients will be eligible if they are untreated
- Patients must have an indication for treatment by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- Patients must be age >= 18 years at the time of signing informed consent, understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug; women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate
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- Alanine aminotransferase (ALT) =< 2.5 x ULN
- Estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft-Gault equation unless disease related
- Free of prior malignancies for 3 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast, who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 3 years prior to study enrollment; if patients have another malignancy that was treated within the last 3 years, such patients can be enrolled, after consultation with the principal investigator, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center
- A urine pregnancy test (within 7 days of enrollment date) is required for women with childbearing potential
Who cannot join
- Pregnant or breast-feeding females
- Prior therapy with ibrutinib or other kinase inhibitors that target Bruton's tyrosine kinase (BTK); patients who previously received therapy with the phosphoinositide-3 kinase (PI3K) delta inhibitor idelalisib (Zydelig) are allowed to be enrolled
- Treatment including chemotherapy, chemo-immunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial
- Investigational agent received within 30 days prior to the first dose of study drug
- Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP)
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- Patients with severe hematopoietic insufficiency, as defined by an absolute neutrophil count of less than 500/uL, unless disease-related, and/or a platelet count of less than 30,000/uL at time of screening for this protocol
- Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with ibrutinib and rituximab
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- History of stroke or cerebral hemorrhage within 6 months
- Evidence of bleeding diathesis or coagulopathy within 3 months
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment date, anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to enrollment date; bone marrow aspiration and/or biopsy are allowed
- Serious, non-healing wound, ulcer, or bone fracture
- Treatment with Coumadin; patients who recently received Coumadin must be off Coumadin for at least 7 days prior to start of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ibrutinib vs Ibrutinib + Rituximab (i vs iR) in Patients With Relapsed (CLL)
This phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.
Read the detailed description
PRIMARY OBJECTIVE:
- To compare the 2-year progression-free survival (PFS) rate in treated patients.
SECONDARY OBJECTIVE:
- To determine safety and tolerability, the overall response rate (ORR), the estimated PFS, changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels) and biomarker responses in relapsed chronic lymphocytic leukemia (CLL) patients receiving ibrutinib (i) versus ibrutinib and rituximab (iR).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab intravenously (IV) over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 60 days and then every 4 months for 5 years.
- Conditions
- Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma
- Medical subject headings
- Leukemia, Prolymphocytic, 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 BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (ibrutinib) | Experimental | Patients receive ibrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ibrutinib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm II (ibrutinib, rituximab) | Experimental | Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab IV over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ibrutinib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival rate
A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
Measured: Time from start of treatment to progression or death date, assessed at 2 years
Secondary outcomes (5)
Incidence of adverse events
Toxicity will be reported by type, frequency and severity. Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements.
Measured: Up to 5 years
Overall response rate
Wilcoxon rank test will be used in the data analyses of continuous variables.
Measured: Up to 5 years
Estimated progression-free survival
Time to progression functions will be estimated using the Kaplan-Meier method. A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
Measured: Up to 5 years
Changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels)
Will be assessed by flow cytometry.
Measured: Baseline to up to 5 years
Quality of life (QOL)
Will be assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30). Analyzed by linear mixed models for longitudinal data. These models allow each patient to have a random intercept and a random slope, which describe their differences at baseline and their different changing trends over time.
Measured: Up to 24 cycles (96 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2013 (estimated)
- Study start6 Dec 2013
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prolymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jan A Burger, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02007044
- Sponsor's protocol ID
- 2013-0703
- Other IDs
- NCI-2014-00989, NCI-2014-00843, 2013-0703
- Status last verified
- Jun 2026
- First submitted
- 5 Dec 2013
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Burger JA, Sivina M, Jain N, Kim E, Kadia T, Estrov Z, Nogueras-Gonzalez GM, Huang X, Jorgensen J, Li J, Cheng M, Clow F, Ohanian M, Andreeff M, Mathew T, Thompson P, Kantarjian H, O'Brien S, Wierda WG, Ferrajoli A, Keating MJ. Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2019 Mar 7;133(10):1011-1019. doi: 10.1182/blood-2018-10-879429. Epub 2018 Dec 7.
PubMed 30530801
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ibrutinib vs Ibrutinib + Rituximab (i vs iR) in Patients With Relapsed (CLL)
- ClinicalTrials.gov ID
- NCT02007044
- Acronym / sponsor ID
- 2013-0703
- Conditions
- Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 66 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 6 Dec 2013 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 10 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.
Detailed description
PRIMARY OBJECTIVE:
- To compare the 2-year progression-free survival (PFS) rate in treated patients.
SECONDARY OBJECTIVE:
- To determine safety and tolerability, the overall response rate (ORR), the estimated PFS, changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels) and biomarker responses in relapsed chronic lymphocytic leukemia (CLL) patients receiving ibrutinib (i) versus ibrutinib and rituximab (iR).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab intravenously (IV) over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 60 days and then every 4 months for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (ibrutinib) | Experimental | Drug: Ibrutinib, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive ibrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm II (ibrutinib, rituximab) | Experimental | Drug: Ibrutinib, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Biological: RituximabPatients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab IV over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have a diagnosis of CLL/small lymphocytic lymphoma (SLL) or prolymphocytic leukemia (PLL) and be previously treated; given the poor outcome of CLL/SLL/PLL patients with 17p deletion (del) or tumor protein (TP)53 mutation to standard frontline chemo-immunotherapy, such patients will be eligible if they are untreated
- Patients must have an indication for treatment by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- Patients must be age >= 18 years at the time of signing informed consent, understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug; women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
Key exclusion criteria (15 listed)
- Pregnant or breast-feeding females
- Prior therapy with ibrutinib or other kinase inhibitors that target Bruton's tyrosine kinase (BTK); patients who previously received therapy with the phosphoinositide-3 kinase (PI3K) delta inhibitor idelalisib (Zydelig) are allowed to be enrolled
- Treatment including chemotherapy, chemo-immunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial
- Investigational agent received within 30 days prior to the first dose of study drug
- Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
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: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Arm I (ibrutinib), Arm II (ibrutinib, rituximab) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (ibrutinib), Arm II (ibrutinib, rituximab) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (ibrutinib), Arm II (ibrutinib, rituximab) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Arm II (ibrutinib, rituximab) |
Primary outcome
Progression-free survival rate
Time frame: Time from start of treatment to progression or death date, assessed at 2 years
A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
5 secondary outcomes
Incidence of adverse events
Time frame: Up to 5 years
Overall response rate
Time frame: Up to 5 years
Estimated progression-free survival
Time frame: Up to 5 years
Changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels)
Time frame: Baseline to up to 5 years
Quality of life (QOL)
Time frame: Up to 24 cycles (96 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Derived from this study: PubMed 30530801Burger JA, Sivina M, Jain N, Kim E, Kadia T, Estrov Z, Nogueras-Gonzalez GM, Huang X, Jorgensen J, Li J, Cheng M, Clow F, Ohanian M, Andreeff M, Mathew T, Thompson P, Kantarjian H, O'Brien S, Wierda WG, Ferrajoli A, Keating MJ. Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2019 Mar 7;133(10):1011-1019. doi: 10.1182/blood-2018-10-879429. Epub 2018 Dec 7.
- MD Anderson Cancer CenterLink provided by the sponsor.
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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.
Jan A Burger principal investigator
M.D. Anderson Cancer Center
1 site 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, Quality-of-Life Assessment and Questionnaire Administration in people with Prolymphocytic Leukemia and Recurrent Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center 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 10 inclusion and 15 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 22 Jun 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?
This study is still under way. Results are not available in the source record yet.
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?
Progression-free survival rate (time frame: Time from start of treatment to progression or death date, assessed at 2 years). 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 NCT02007044, 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 22 Jun 2026.