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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor:
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT01625741
First received: June 6, 2012
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • rate of conversion into Minimal Residual Disease negativity [ Time Frame: Month 7 (= 3 months after the last dose of rituximab) ] [ Designated as safety issue: No ]
    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:
  • 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic/Pharmacodynamic correlation [ Time Frame: month 7 ] [ Designated as safety issue: No ]
    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.

  • quality of life study [ Time Frame: during 17 months ] [ Designated as safety issue: No ]
    from selection visit until last follow-up visit planned 1 years after the last rituximab perfusion


Estimated Enrollment: 30
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab
4 monthly administrations of rituximab
Drug: Rituximab
2000 mg, IV, monthly, for 4 months (= 4 doses)
Other Name: Mabthera

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625741

Contacts
Contact: Eric Van Den Neste, MD, PhD +32 27 64 18 75 eric.vandenneste@uclouvain.be
Contact: Sabrina Costantini, Ms +32 27 64 18 09 sabrina.costantini@uclouvain.be

Locations
Belgium
ZNA Middelheim Not yet recruiting
Antwerpen, Belgium, 2020
Contact: Karolien Beel, MD       Karolien.Beel@zna.be   
Principal Investigator: Karolien Beel, MD         
Clinique Sud Luxembourg Not yet recruiting
Arlon, Belgium, 6700
Contact: Pascal Pierre, MD       ppierre@clinsudlux.be   
Principal Investigator: Pascal Pierre, MD         
AZ Sint-Jan Not yet recruiting
Brugge, Belgium, 8000
Contact: Achiel Van Hoof, MD, PhD       Achiel.VanHoof@azbrugge.be   
Principal Investigator: Achiel Van Hoof, MD, PhD         
ULB Erasme Not yet recruiting
Brussels, Belgium, 1070
Contact: Marie Maerevoet, MD       marie.maerevoet@yahoo.fr   
Principal Investigator: Marie Maerevoet, MD         
Cliniques universitaires Saint Luc Not yet recruiting
Brussels, Belgium, 1200
Contact: Eric Van Den Neste, Md, PhD    +32 27 64 18 75    eric.vandenneste@uclouvain.be   
Principal Investigator: Eric Van Den Neste, MD, PhD         
Clinique Saint Jean Not yet recruiting
Brussels, Belgium, 1000
Contact: Déborah Bauwens, MD       dbauwens@clstjean.be   
Principal Investigator: Déborah Bauwens, MD         
Grand Hôpital de Charleroi Not yet recruiting
Charleroi, Belgium, 6000
Contact: Delphine Pranger, MD       pranger.delphine@ghdc.be   
Principal Investigator: Delphine Pranger, MD         
UZ Gent Not yet recruiting
Gent, Belgium, 9000
Contact: Fritz Offner, MD, PhD       fritz.offner@ugent.be   
Principal Investigator: Firtz Offner, MD, PhD         
Hôpital de Jolimont Not yet recruiting
Haine-Saint-Paul, Belgium, 7100
Contact: Vanessa Delrieu, MD       vdelrieu@ulb.ac.be   
Principal Investigator: Vanessa Delrieu, Md         
KUL Gasthuisberg Not yet recruiting
Leuven, Belgium, 3000
Contact: Ann Janssens, MD, PhD       Ann.Janssens@uz.kuleuven.ac.be   
Principal Investigator: Ann Janssens, MD, PhD         
CHU ULg Sart Tilman Not yet recruiting
Liège, Belgium, 4000
Contact: Bernard De Prijck, MD       bernard.deprijck@chu.ulg.ac.be   
Principal Investigator: Bernard De Prijck, MD         
CHR Clinique Saint Joseph Not yet recruiting
Mons, Belgium, 7000
Contact: Dominique Boulet, MD       dominique.boulet@chr-afic.be   
Principal Investigator: Dominique Boulet, MD         
Clinique Saint Pierre Not yet recruiting
Ottignies, Belgium, 1340
Contact: Thierry Connerotte, MD       th.connerotte@clinique-saint-pierre.be   
Principal Investigator: Thierry Connerotte, MD         
Heilig-Hartziekenhuis Not yet recruiting
Roeselaere, Belgium, 8800
Contact: Hilde Demuynck, MD       HDemuynck@hhr.be   
Principal Investigator: Hilde Demuynck, MD         
Clinique universitaire de Mont Godinne Not yet recruiting
Yvoir, Belgium, 5530
Contact: Marc André, Md       marc.andre@uclouvain.be   
Principal Investigator: Marc André, Md         
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
Principal Investigator: Eric Van Den Neste, MD, PhD Cliniques universitaires Saint-Luc
  More Information

No publications provided

Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT01625741     History of Changes
Other Study ID Numbers: HYDRIC
Study First Received: June 6, 2012
Last Updated: June 19, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Ethics Committee

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

ClinicalTrials.gov processed this record on August 27, 2014