NCT02048813|Active Not RecruitingPhase 3Results

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

A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

National Cancer Institute (NCI)ClinicalTrials.gov

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7 other identifiers

NCI-2014-00118E1912ECOG-E1912R01CA193541U10CA021115U10CA180820U24CA196172

Study Type

interventional

Target

529

Locations

1 country

Sites

783

Timeline

RegisteredJan 2014

StartedMar 2014

CompletionOct 2026

Brief Summary

This phase III trial studies ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. It is not yet known whether fludarabine phosphate, cyclophosphamide, and rituximab may work better than ibrutinib and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

529

participants targeted

Target at P75+ for phase_3

Timeline

5mo left

Started Mar 2014

Longer than P75 for phase_3

Geographic Reach

1 country

783 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.6 years study duration

Study Progress97%

Mar 2014Oct 2026

First Submitted

Initial submission to the registry

January 27, 2014

Completed

2 days until next milestone

First Posted

Study publicly available on registry

January 29, 2014

Completed

1 month until next milestone

Study Start

First participant enrolled

March 10, 2014

Completed

4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 24, 2018

Completed

4.8 years until next milestone

Results Posted

Study results publicly available

August 14, 2023

Completed

3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 9, 2026

Expected

Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

4.6 years

First QC Date

January 27, 2014

Results QC Date

May 17, 2023

Last Update Submit

April 30, 2026

Conditions

Anemia Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS) Rate at 3 Years
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.
Assessed every 3 months until progression up to 4 years and 8 months

Secondary Outcomes (5)

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
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) Score at 12 Months
Assessed at 12 months
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
Progression-free Survival (PFS) by Measurable Residual Disease (MDR) Status at 2 Years
Assessed every 3 months until progression up to 5 years

Other Outcomes (6)

Distribution of Genetic Abnormalities Before and After Treatment
Assessed at baseline, and 3, 6, 12, 15, 18, 24, 36 months
T-cell Counts at 12 Months
Assessed at 12 months
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
+3 more other outcomes

Study Arms (2)

Arm A (ibrutinib, rituximab)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-28. Beginning cycle 2, patients also receive rituximab IV over 4 hours on days 1 and 2 of cycle 2, and day 1 of cycles 3-7. Treatment repeats every 28 days for 7 cycles in the absence of unacceptable toxicity. In the absence of disease progression, patients may continue ibrutinib PO QD for a maximum of 10 years.

Drug: IbrutinibOther: Laboratory Biomarker AnalysisOther: Pharmacogenomic StudyOther: Quality-of-Life AssessmentBiological: Rituximab

Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

ACTIVE COMPARATOR

Patients receive rituximab IV over 4 hours on days 1 and 2 of cycle 1, and day 1 of cycles 2-6. Patients also receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 30 minutes on days 1-3. Treatment repeats every 28 days for 6 cycles in the absence of unacceptable toxicity.

Drug: CyclophosphamideDrug: Fludarabine PhosphateOther: Laboratory Biomarker AnalysisOther: Pharmacogenomic StudyOther: Quality-of-Life AssessmentBiological: Rituximab

Interventions

CyclophosphamideDRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

Fludarabine PhosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

IbrutinibDRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765, Imbruvica, PCI 32765, PCI-32765, PCI32765

Arm A (ibrutinib, rituximab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm A (ibrutinib, rituximab)Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

Pharmacogenomic StudyOTHER

Correlative studies

Also known as: PHARMACOGENOMIC

Arm A (ibrutinib, rituximab)Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (ibrutinib, rituximab)Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

RituximabBIOLOGICAL

Given IV

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Arm A (ibrutinib, rituximab)Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

Eligibility Criteria

Age18 Years - 70 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of:
Biopsy-proven small lymphocytic lymphoma or
Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following:
Peripheral blood lymphocyte count of greater than 5 x 10\^9/L
Immunophenotype consistent with CLL defined as:
The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation \[CD\]19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)
Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression)
Negative FISH analysis for t(11;14)(immunoglobulin heavy locus \[IgH\]/cyclin D1 \[CCND1\]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLL
Has met at least one of the following indications for treatment:
Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin \[Hg\] \< 11 g/dl) and/or thrombocytopenia (platelets \< 100 x 10\^9/L)
Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
One or more of the following disease-related symptoms:
Weight loss \>= 10% within the previous 6 months
Grade 2 or 3 fatigue attributed to CLL
+50 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (783)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC