NCT01886872|Active Not RecruitingPhase 3Results

Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (≥ 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

National Cancer Institute (NCI)ClinicalTrials.gov

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7 other identifiers

NCI-2013-01220ALLIANCE A041202A041202K23CA178183R01CA183444U10CA031946U10CA180821

Study Type

interventional

Target

547

Locations

2 countries

Sites

940

Timeline

RegisteredJun 2013

StartedJan 2014

CompletionJun 2026

Brief Summary

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Chemotherapy drugs, such as bendamustine hydrochloride, 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. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

Trial Health

On Track

Trial Health Score

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

Enrollment

547

participants targeted

Target at P75+ for phase_3

Timeline

1mo left

Started Jan 2014

Longer than P75 for phase_3

Geographic Reach

2 countries

940 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

12.4 years study duration

Study Progress99%

Jan 2014Jun 2026

First Submitted

Initial submission to the registry

June 24, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

June 26, 2013

Completed

7 months until next milestone

Study Start

First participant enrolled

January 15, 2014

Completed

4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 7, 2018

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

December 30, 2019

Completed

6.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 7, 2026

Expected

Last Updated

May 4, 2026

Status Verified

December 1, 2025

Enrollment Period

4.6 years

First QC Date

June 24, 2013

Results QC Date

September 30, 2019

Last Update Submit

May 1, 2026

Conditions

Stage IV Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

Progression Free Survival (PFS)
The Kaplan-Meier method will be used to estimate the progression free survival distributions for each arm, with median estimates provided. Progression is defined as any one of the following: an increase in number of blood lymphocytes by \>= 50% with \>= 5000 B lymphocytes/mL in patients on Arm A or those on Arms 2 or 3 no longer receiving ibrutinib, \>= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, \>= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels \> 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first.
Time from study entry to the time of documented disease progression or death. The analysis was event driven, performed at 2.5 years after the last patient enrolled;up to 4 years.

Secondary Outcomes (8)

Progression Free Survival (PFS) Rate at 2 Years
Time from study entry to the time of documented disease progression or death, assessed up to 2 years
Overall Survival (OS) at 2 Years
From the date of registration to the date of death, assessed up to 2 years
Duration of Response (DOR) (Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL)
From the date of first response until progression or death, performed at 2.5 years after the last patient enrolled; up to 4 years.
Percentage of Patients Achieving Any Response to Treatment (Overall Response Rate [ORR] [Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL])
Performed at 2.5 years after the last patient enrolled;up to 4 years.
Percentage of Patients Achieving a Biopsy-proven Complete Response (CR)
Performed at 2.5 years after the last patient enrolled; up to 4 years.
+3 more secondary outcomes

Other Outcomes (1)

Geriatric Functional Status (Optional)
Performed at 2.5 years after the last patient enrolled

Study Arms (3)

Arm I (rituximab, bendamustine hydrochloride)

ACTIVE COMPARATOR

Patients receive rituximab IV on day 1 (day 0 course 1) and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II. Additionally, patients undergo bone marrow aspiration and biopsy, blood sample collection, and CT throughout the study.

Drug: Bendamustine HydrochlorideProcedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Computed TomographyOther: Laboratory Biomarker AnalysisOther: Quality-of-Life AssessmentBiological: Rituximab

Arm II (ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy, blood sample collection, and CT throughout the study.

Procedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Computed TomographyDrug: IbrutinibOther: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment

Arm III (ibrutinib, rituximab)

EXPERIMENTAL

Patients receive ibrutinib as in Arm II. Patients receive rituximab IV on days 1, 8, 15, and 22 of course 2 and on day 1 of courses 3-6. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy, blood sample collection, and CT throughout the study.

Interventions

Bendamustine HydrochlorideDRUG

Given IV

Also known as: Belrapzo, Bendamustin Hydrochloride, Bendeka, CEP 18083, CEP-18083, CEP18083, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treakisym, Treanda, VIVIMUSTA

Arm I (rituximab, bendamustine hydrochloride)

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

Bone Marrow AspirationPROCEDURE

Undergo bone marrow aspiration and biopsy

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

Bone Marrow BiopsyPROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

Computed TomographyPROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

IbrutinibDRUG

Given PO

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

Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (rituximab, bendamustine hydrochloride)Arm II (ibrutinib)Arm III (ibrutinib, rituximab)

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 I (rituximab, bendamustine hydrochloride)Arm III (ibrutinib, rituximab)

Eligibility Criteria

Age65 Years+

Sexall

Healthy VolunteersNo

Age GroupsOlder Adult (65+)

You may qualify if:

PRE-REGISTRATION (STEP 0)
All patients are REQUIRED to be pre-registered to A041202 in order to submit peripheral blood to the Alliance Hematologic Malignancy Biorepository (HEME) for central Zap-70 methylation. This specimen submission is mandatory prior to registration as results will be used for stratification
REGISTRATION (STEP 1)
Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:
\>= 5 x 10\^9 B lymphocytes (5000/uL) in the peripheral blood
On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in \> 10% of cells must lack t(11;14) translocation by interphase cytogenetics
Patients must be intermediate or high-risk Rai stage CLL
Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly
High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin \< 11 g/dL) or thrombocytopenia (platelet count \< 100 x 10\^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia
Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which includes at least one of the following criteria:
Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
+29 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (940)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC