CHAIROS Study A Study of MabThera/Rituxan (Rituximab) Maintenance Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Naive to Chemotherapy

CHAIROS - Effect of Early Brief Intensification by Chemoimmunotherapy With FCR Followed by FR and Rituximab Maintenance on Clinical Response in Chemo-naïve Patients With B-CLL

This study will evaluate the efficacy and safety of intense combination treatment including MabThera/Rituxan (rituximab), followed by MabThera/Rituxan maintenance therapy in patients with B-cell CLL who are naive to chemotherapy. The anticipated time on study treatment is 2.5 years.

Study Overview

• Status: Completed
• Conditions: Lymphocytic Leukemia, Chronic
• Intervention / Treatment: Drug: rituximab [MabThera/Rituxan]; Drug: fludarabine; Drug: cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie
  • Leoben, Austria, 8700
    • LKH Hochsteiermark; Abt. für Innere Medizin
  • Linz, Austria, 4010
    • Kh Der Barmherzigen Schwestern; Interne I X
  • Linz, Austria, 4020
    • A.Ö. Krankenhaus Der Elisabethinen Linz; I. Interne Abt.
  • Linz, Austria, 4020
    • Kepler Universitätskliniken GmbH - Med Campus III; I. Medizinische Abteilung
  • Rankweil, Austria, 6830
    • Landeskrankenhaus Rankweil; Interne E
  • Salzburg, Austria, 5020
    • Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
  • Wels, Austria, 4600
    • Klinikum Kreuzschwestern Wels; Iii. Interne Abt.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• B-cell CLL
• No previous chemotherapy, radiotherapy, or immunotherapy

Exclusion Criteria:

• Reduced organ function, or bone marrow dysfunction not due to CLL
• Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer
• Patients with a history of severe cardiac disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MabThera/Rituxan	Drug: rituximab [MabThera/Rituxan]; Every 4 weeks for 6 cycles of induction, followed by maintenance therapy every 3 months x 8; Drug: fludarabine; Every 4 weeks, 6 cycles; Drug: cyclophosphamide; Every 4 weeks, 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Best Clinical Response of Clinical Remission (CR)	Best clinical response was determined according to the National Cancer Institute (NCI) Clinical and Clinical plus (+) Radiological evaluations by central response assessment. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of chronic lymphocytic lymphoma (CLL) with additional computerized tomography (CT) scan evaluation of lymphadenopathy. Per NCI guidelines, CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils greater than (>)1500 per microliter (/µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 grams per deciliter (g/dL), lymphocytes (LC) (less than) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC.	Weeks 1, 5, 9, 12, 13, 17, 21 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment)	Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, partial remission (PR), partial remission with toxicity associated (PRTox), progressive disease (PD), and stable disease (SD) were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). Last observation carried forward (LOCF) method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.	Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment)	Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, PR, PRTox, PD, and SD were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). LOCF method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.	Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)
Time to Next Treatment - Percentage of Participants With an Event	Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.	Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months
Time to Next Treatment - Time to Event	Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.	Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months
Percentage of Participants With Adverse Events (AEs)	AEs were recorded from the date of first medication administration until 28 days after the last trial medication.	Day 1 of Cycles 1, 2, 3, 4, 5, and 6 to 28 days after the last trial medication.

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2005
• Primary Completion (Actual): September 24, 2012
• Study Completion (Actual): September 24, 2012

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: ML18434