Phase II Study of High-Dose Rituximab in High-Risk Chronic Lymphocytic Leukemia Patients in Suboptimal Response After Induction Immunochemotherapy (HYDRIC)

September 28, 2015 updated by: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
This study explores the potential to improve the quality of response obtained after induction treatment in Chronic Lymphocytic Leukemia (CLL), by giving a short and intense consolidation schema using high-dose rituximab. Patients in suboptimal response (Minimal Residual Disease persistence) after induction will be selected, as well as those who have a Minimal Residual Disease (MRD) relapse after having achieved MRD negativity.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study is reserved for patients with residual disease at the end of therapy at the level of Minimal Residual Disease (MRD-positive either in the peripheral blood at least 6 months after the last dose of rituximab-containing immunochemotherapy or in the bone marrow at least 3 months after the last dose of rituximab-containing immunochemotherapy). Patients who have achieved MRD eradication and who have MRD relapse (reappearance of residual leukemic cells using 7/8-color flow cytometry in peripheral blood or bone marrow) are also eligible for the study.

Rituximab will be given intravenously at a monthly dose of 2000 mg four months (in total 4 doses of 2000 mg each), starting within one month after informed consent signature.

The patients will be followed during the treatment period with rituximab. A final evaluation will be done 3 months after the last dose of rituximab.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium, 2020
        • ZNA Middelheim
      • Arlon, Belgium, 6700
        • Clinique Sud Luxembourg
      • Brugge, Belgium, 8000
        • AZ Sint-Jan
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint Luc
      • Brussels, Belgium, 1070
        • ULB Erasme
      • Brussels, Belgium, 1000
        • Clinique Saint Jean
      • Charleroi, Belgium, 6000
        • Grand Hôpital de Charleroi
      • Gent, Belgium, 9000
        • UZ Gent
      • Haine-Saint-Paul, Belgium, 7100
        • Hopital de Jolimont
      • Leuven, Belgium, 3000
        • KUL Gasthuisberg
      • Liège, Belgium, 4000
        • CHU ULg Sart Tilman
      • Mons, Belgium, 7000
        • CHR Clinique Saint Joseph
      • Ottignies, Belgium, 1340
        • Clinique Saint Pierre
      • Roeselaere, Belgium, 8800
        • Heilig-Hartziekenhuis
      • Yvoir, Belgium, 5530
        • Clinique Universitaire de Mont Godinne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • B-cell Chronic Lymphocytic Leukemia defined by standard NCI criteria in first line or in relapse
  • > 18 years-old

  • Presence of Minimal Residual Disease (MRD positivity) by Flow Cytometry criteria in these two clinical situations :

    1. Patients in Complete Remission (defined by standard criteria including Bone Marrow examination) after rituximab-containing immunochemotherapy (ICT), who show persisting MRD either in the Peripheral Blood at least 6 months after the last dose of rituximab-containing immunochemotherapy or in the Bone Marrow at least 3 months after the last dose of rituximab-containing ICT
    2. Patients in continuous CR who show MRD relapse in PB or BM without clinical progression (as defined by NCI) at any time after ICT

  • ICT should have comprised:

    1. Rituximab combined with fludarabine, with or without an alkylating drug, with or without an anthracycline (ex: Fludarabine-Rituximab, Fluda-Cyclophsphamide-Rituximab, FCR-Mitoxantrone, R-bendamustine…)
    2. At least 4 cycles
  • Patients should have recovered from the toxicities of ICT
  • POOR PROGNOSTIC FEATURES (before induction ICT) defined by at least one of the following markers: stage C Binet, unmutated IgVH genes, 17p deletion, 11q deletion, Zap-70 positivity, high CD38, mutated IgVH genes if VH3-21 usage
  • In addition, in patients with 11q deletion and/or presence of bulky lymph nodes prior to induction therapy, absence of profound lymph nodes at response evaluation should have been confirmed by CT scan
  • CIRS ≤6
  • Absence of significant geriatric syndromes and/or significant limitations in instrumental activities of daily living (IADL)
  • Performance status (ECOG) < 2
  • Neutrophils > 1000/microL, platelets > 100,000/microL
  • Creatinine clearance > 50 ml/min (clearance can be reevaluated after adequate hydration of the patient)
  • Patient's written informed consent

Exclusion Criteria:

  • Less than CR defined by standard criteria response after ICT
  • Ongoing active infections (bacterial, viral or fungal)
  • Known infection with HIV
  • Subjects with any serological evidence of current or past hepatitis B or hepatitis C exposure are excluded unless the serological findings are clearly due to vaccination.
  • Concomitant treatment with steroids, or any immunosuppressive drug
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Transformation into an aggressive B-cell malignancy (eg. diffuse large B-cell lymphoma, Hodgkin lymphoma)
  • Pregnancy, breast feeding, female patients with childbearing potential or male patients who are unwilling to use adequate contraception
  • Intolerance to rituximab
  • Concomitant severe disease (uncompensated cardiac insufficiency, severe respiratory insufficiency…)
  • Severe hypogammaglobulinemia with recurrent infections, unless the patient is receiving substitutive IV immunoglobulins
  • Transaminases (AST, ALT) > 3 xULN
  • Conjugated bilirubin > 2 xULN
  • Prior autologous stem cell transplantation less than 12 months
  • Prior allogeneic stem cell transplantation
  • Central Nervous System involvement
  • Any coexisting medical or psychological condition that would preclude participation to the required study procedures
  • Prior history of malignancies, other than CLL, unless subject has been free of the disease for > 4 years. Exceptions include the following: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding prostate cancer (TNM stage of T1a or T1b)
  • Participation in any clinical study or having taken any investigational therapy which would interfere with the study drug for a disease other than CLL, within 28 days prior to initiating the maintenance therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rituximab
4 monthly administrations of rituximab
Drug: Rituximab
2000 mg, IV, monthly, for 4 months (= 4 doses)
Other Names:
  • Mabthera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rate of conversion into Minimal Residual Disease negativity
Time Frame: Month 7 (= 3 months after the last dose of rituximab)
Evaluate the rate of conversion into MRD negativity 3 months after the administration of 4 monthly courses of high-dose (2000 mg) rituximab in high-risk CLL patients with suboptimal response after immunochemotherapy (ICT), or MRD relapse after ICT.
Month 7 (= 3 months after the last dose of rituximab)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
toxicity of the consolidation treatment by rituximab
Time Frame: from first administration of rituximab until end of follow-up period (= 12 months after the last rituximab administration)
from first administration of rituximab until end of follow-up period (= 12 months after the last rituximab administration)
Pharmacokinetic/Pharmacodynamic correlation
Time Frame: month 7
correlation between the level of MRD conversion at month 7 and pharmacokinetic dosage of rituximab performed after each rituximab perfusions, 1 month and 3 months after last rituximab.
month 7
quality of life study
Time Frame: during 17 months
from selection visit until last follow-up visit planned 1 years after the last rituximab perfusion
during 17 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Investigators

  • Principal Investigator: Eric Van Den Neste, MD, PhD, Cliniques Universitaires Saint-Luc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

June 6, 2012

First Submitted That Met QC Criteria

June 19, 2012

First Posted (Estimate)

June 21, 2012

Study Record Updates

Last Update Posted (Estimate)

September 29, 2015

Last Update Submitted That Met QC Criteria

September 28, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HYDRIC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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