Trial · NCT02048813

Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT02048813, Phase 3, Active not recruiting, National Cancer Institute (NCI); results first posted 2023-08-14

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. Trials, record NCT02048813. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02048813

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT number: NCT02048813
Status: Active not recruiting
Phases: Phase 3
Enrollment: 529 participants, actual
Lead sponsor: National Cancer Institute (NCI)
Conditions: Anemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Interventions: Cyclophosphamide, Fludarabine Phosphate, Ibrutinib, Laboratory Biomarker Analysis, Pharmacogenomic Study, Quality-of-Life Assessment, Rituximab
First posted: 2014-01-29
Last updated: 2026-08-28
Results first posted: 2023-08-14

Source ClinicalTrials.gov

Registered outcomes12

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Progression-free Survival (PFS) Rate at 3 Years	Assessed every 3 months until progression up to 4 years and 8 months	PFS was defined as the time from randomization to CLL progression or death, whichever occurred first. Progression is characterized by any of the following: * ≥ 50% increase from nadir since start of treatment (tx) in the sum of the products of at least 2 lymph nodes on 2 consecutive examinations 2 weeks apart * ≥ 50% increase from nadir since start of tx in the size of liver and/or spleen * ≥ 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be ≥ 5x10\^9/L to qualify as disease progression. * Transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with \> 55% prolymphocytes). For patients who achieve a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count \> 5x10\^9/L and/or recurrence of palpable lymphadenopathy \> 1.5 cm by physical exam.
Secondary	Overall Survival (OS) Rate at 3 Years	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5, up to 4 years and 8 months	Overall survival was defined as time from randomization to death from any cause or date last known alive. Overall survival rate at 3 years was estimated using the method of Kaplan-Meier.
Secondary	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 6 Months	Assessed at 6 months	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) is comprised of the physical well-being (PWB) and functional well-being (FWB) components of the FACT-General (FACT-G) and the leukemia subscale. The FACT-Leu TOI contains a total of 31 items, with scores ranging from 0 to 124. The higher the score, the better the quality of life (QOL).
Secondary	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 12 Months	Assessed at 12 months	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) is comprised of the physical well-being (PWB) and functional well-being (FWB) components of the FACT-General (FACT-G) and the leukemia subscale. The FACT-Leu TOI contains a total of 31 items, with scores ranging from 0 to 124. The higher the score, the better the quality of life (QOL).
Secondary	The Association Between Baseline Rai Stage and Complete Response (CR) Rate	Assessed at baseline, every 3 months for the first 2 years, and every 6 months for years 3-5	Patients are classified as stage 0-IV according to the Rai system and categorized into one of the three risk groups: Low risk - Stage 0 Intermediate risk - Stage I or II High risk - Stage III or IV CR requires all of the following for at least 2 months: * Absence of lymphadenopathy by physical examination on 2 occasions at least 4 weeks apart and appropriate radiographic techniques. For patients whose only measurable disease at the time of enrollment is on CT scan, a CT scan is required and all lymph nodes must be ≤ 1.5 cm before classifying the patient a CR. * Absence of hepatomegaly or splenomegaly by physical examination * Absence of constitutional symptoms due to disease * Normal complete blood count * One marrow aspirate and biopsy should be performed 52 weeks after Day 1 of cycle 1 among patients with clinical and laboratory evidence of a CR to document a CR. The marrow sample must be at least normocellular with \< 30% of nucleated cells being lymphocytes.
Secondary	Progression-free Survival (PFS) by Measurable Residual Disease (MDR) Status at 2 Years	Assessed every 3 months until progression up to 5 years	PFS was defined as time from randomization to progression or death. Progression is characterized by any of the following: * ≥ 50% increase from nadir since start of treatment (tx) in the sum of the products of ≥ 2 lymph nodes on 2 consecutive exams 2 weeks apart * ≥ 50% increase from nadir since start of tx in the size of liver and/or spleen * ≥ 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be ≥ 5x10\^9/L to qualify as progression. * Transformation to a more aggressive histology. For patients with a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count \> 5x10\^9/L and/or recurrence of palpable lymphadenopathy \>1.5 cm by physical exam. MRD status was evaluated at 2 years and samples with \<=20 monotypic events or an MRD level of \<10\^-4 were classified as undetectable MRD.
Other	Distribution of Genetic Abnormalities Before and After Treatment	Assessed at baseline, and 3, 6, 12, 15, 18, 24, 36 months	Genetic abnormalities are assessed at baseline and longitudinally during treatment as well as after treatment. Distribution of genetic abnormalities are reported.
Other	T-cell Counts at 12 Months	Assessed at 12 months	T-cell counts will be measured at 12 months.
Other	Association Between Single Nucleotide Polymorphisms (SNPs) and PFS	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5	PFS was defined as time from randomization to progression or death, whichever occurred first. Progression is characterized by any of the following: * ≥ 50% increase from nadir since start of treatment (tx) in the sum of the products of ≥2 lymph nodes on 2 consecutive examinations 2 weeks apart * ≥ 50% increase from nadir since start of tx in the size of liver and/or spleen * ≥ 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be ≥ 5x10\^9/L to qualify as progression. * Transformation to a more aggressive histology. For patients who achieve a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count \> 5x10\^9/L and/or recurrence of palpable lymphadenopathy \> 1.5 cm by physical exam. The distribution of PFS by SNPs will be reported.
Other	Prognostic Model to Predict PFS	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5	A prognostic model that incorporates clinical and biologic characters to predict PFS will be developed.

1 to 10 of 12Source ClinicalTrials.gov

See all 12 registered outcomes

Outcomes12

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Progression-free Survival (PFS) Rate at 3 Years	Assessed every 3 months until progression up to 4 years and 8 months	All randomized patients were included in this analysis.	Proportion of participants	NUMBER
SECONDARY	Overall Survival (OS) Rate at 3 Years	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5, up to 4 years and 8 months	All randomized patients were included in this analysis.	Proportion of participants	NUMBER
SECONDARY	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 6 Months	Assessed at 6 months
SECONDARY	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 12 Months	Assessed at 12 months
SECONDARY	The Association Between Baseline Rai Stage and Complete Response (CR) Rate	Assessed at baseline, every 3 months for the first 2 years, and every 6 months for years 3-5
SECONDARY	Progression-free Survival (PFS) by Measurable Residual Disease (MDR) Status at 2 Years	Assessed every 3 months until progression up to 5 years
OTHER_PRE_SPECIFIED	Distribution of Genetic Abnormalities Before and After Treatment	Assessed at baseline, and 3, 6, 12, 15, 18, 24, 36 months
OTHER_PRE_SPECIFIED	T-cell Counts at 12 Months	Assessed at 12 months
OTHER_PRE_SPECIFIED	Association Between Single Nucleotide Polymorphisms (SNPs) and PFS	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5
OTHER_PRE_SPECIFIED	Prognostic Model to Predict PFS	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5

1 to 10 of 12Source ClinicalTrials.gov

See all 12 outcomes

Results by group4

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Progression-free Survival (PFS) Rate at 3 Years	Arm A (Ibrutinib, Rituximab)	0.894	95% Confidence Interval 0.86 to 0.93	Proportion of participants
Progression-free Survival (PFS) Rate at 3 Years	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	0.729	95% Confidence Interval 0.653 to 0.813	Proportion of participants
Overall Survival (OS) Rate at 3 Years	Arm A (Ibrutinib, Rituximab)	0.988	95% Confidence Interval 0.976 to 1.00	Proportion of participants
Overall Survival (OS) Rate at 3 Years	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	0.915	95% Confidence Interval 0.862 to 0.970	Proportion of participants

Source ClinicalTrials.gov

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Arm A (Ibrutinib, Rituximab)	354
Overall Study	STARTED	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	175
Overall Study	COMPLETED	Arm A (Ibrutinib, Rituximab)	0
Overall Study	COMPLETED	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	105
Overall Study	NOT COMPLETED	Arm A (Ibrutinib, Rituximab)	354
Overall Study	NOT COMPLETED	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	70

Source ClinicalTrials.gov

Adverse events372

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Anemia	Blood and lymphatic system disorders	Arm A (Ibrutinib, Rituximab)	183	352
other	Anemia	Blood and lymphatic system disorders	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	99	158
other	Atrial fibrillation	Cardiac disorders	Arm A (Ibrutinib, Rituximab)	27	352
other	Atrial fibrillation	Cardiac disorders	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	0	158
other	Palpitations	Cardiac disorders	Arm A (Ibrutinib, Rituximab)	30	352
other	Palpitations	Cardiac disorders	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	1	158
other	Chills	General disorders	Arm A (Ibrutinib, Rituximab)	20	352
other	Chills	General disorders	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	17	158
other	Edema limbs	General disorders	Arm A (Ibrutinib, Rituximab)	61	352
other	Edema limbs	General disorders	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	14	158

1 to 10 of 372Source ClinicalTrials.gov

See all 372 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Arm A (Ibrutinib, Rituximab)	4	354
Total, all-cause mortality	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	10	175
Total, other adverse events	Arm A (Ibrutinib, Rituximab)	348	352
Total, other adverse events	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	154	158
Total, serious adverse events	Arm A (Ibrutinib, Rituximab)	270	352
Total, serious adverse events	Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	132	158

Source ClinicalTrials.gov

Papers5

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
31365801	DERIVED	PubMed
33439748	DERIVED	PubMed
34865212	DERIVED	PubMed
35427411	DERIVED	PubMed
37801678	DERIVED	PubMed

Grants4

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

Project	Title	Principal investigators	Organization	Funder	Fiscal years	Source
U10CA180820	ECOG-ACRIN Network Group Operations Center	ODwyer, Peter J; SCHNALL, MITCHELL D.	ECOG-ACRIN MEDICAL RESEARCH FOUNDATION	NATIONAL CANCER INSTITUTE	2014 to 2026	NIH RePORTER
U24CA196172	ECOG-ACRIN Biospecimen Bank to Support NCTN	JEWELL, SCOTT D; HAMILTON, STANLEY R.	ECOG-ACRIN MEDICAL RESEARCH FOUNDATION	NATIONAL CANCER INSTITUTE	2015 to 2025	NIH RePORTER
R01CA193541	Predicting Clinical Outcome After Traditional and Ibrutinib-based Therapy In Chronic Lymphocytic Leukemia	KAY, NEIL E; SHANAFELT, TAIT D	MAYO CLINIC ROCHESTER	NATIONAL CANCER INSTITUTE	2015 to 2019	NIH RePORTER
U10CA021115	Eastern Cooperative Oncology Group Operations Office	COMIS, ROBERT L	FRONTIER SCI & TECHNOLOGY RSCH FDN, INC	NATIONAL CANCER INSTITUTE	1985 to 2013	NIH RePORTER

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Arm A (Ibrutinib, Rituximab) vs Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide): deaths from any cause	Trial comparisons
Arm A (Ibrutinib, Rituximab) vs Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide): serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT02048813

GET https://conductscience.org/api/trials/v1/NCT02048813/events?page=2

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