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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01625741
Recruitment Status : Terminated (Stopped by Principal Investigator decision)
First Posted : June 21, 2012
Last Update Posted : September 29, 2015
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Rituximab Phase 2

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  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of High-Dose Rituximab in High-Risk Chronic Lymphocytic Leukemia Patients in Suboptimal Response After Induction Immunochemotherapy
Study Start Date : July 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Arm Intervention/treatment
Experimental: rituximab
4 monthly administrations of rituximab
Drug: Rituximab
2000 mg, IV, monthly, for 4 months (= 4 doses)
Other Name: Mabthera

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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) ]
  2. 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.

  3. 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

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01625741

ZNA Middelheim
Antwerpen, Belgium, 2020
Clinique Sud Luxembourg
Arlon, Belgium, 6700
AZ Sint-Jan
Brugge, Belgium, 8000
Clinique Saint Jean
Brussels, Belgium, 1000
ULB Erasme
Brussels, Belgium, 1070
Cliniques universitaires Saint Luc
Brussels, Belgium, 1200
Grand Hôpital de Charleroi
Charleroi, Belgium, 6000
UZ Gent
Gent, Belgium, 9000
Hôpital de Jolimont
Haine-Saint-Paul, Belgium, 7100
KUL Gasthuisberg
Leuven, Belgium, 3000
CHU ULg Sart Tilman
Liège, Belgium, 4000
CHR Clinique Saint Joseph
Mons, Belgium, 7000
Clinique Saint Pierre
Ottignies, Belgium, 1340
Roeselaere, Belgium, 8800
Clinique universitaire de Mont Godinne
Yvoir, Belgium, 5530
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Principal Investigator: Eric Van Den Neste, MD, PhD Cliniques universitaires Saint-Luc

Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain Identifier: NCT01625741     History of Changes
Other Study ID Numbers: HYDRIC
First Posted: June 21, 2012    Key Record Dates
Last Update Posted: September 29, 2015
Last Verified: September 2015

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents