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

NCT ID: NCT01625741

Last Updated: 2015-09-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-05-31

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.

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rituximab

4 monthly administrations of rituximab

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

2000 mg, IV, monthly, for 4 months (= 4 doses)

Interventions

Rituximab

2000 mg, IV, monthly, for 4 months (= 4 doses)

Intervention Type: DRUG

Other Intervention Names

Mabthera

Eligibility 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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Van Den Neste, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Locations

ZNA Middelheim

Antwerp, , Belgium

Clinique Sud Luxembourg

Arlon, , Belgium

AZ Sint-Jan

Bruges, , Belgium

Clinique Saint Jean

Brussels, , Belgium

ULB Erasme

Brussels, , Belgium

Cliniques universitaires Saint Luc

Brussels, , Belgium

Grand Hôpital de Charleroi

Charleroi, , Belgium

UZ Gent

Ghent, , Belgium

Hôpital de Jolimont

Haine-Saint-Paul, , Belgium

KUL Gasthuisberg

Leuven, , Belgium

CHU ULg Sart Tilman

Liège, , Belgium

CHR Clinique Saint Joseph

Mons, , Belgium

Clinique Saint Pierre

Ottignies, , Belgium

Heilig-Hartziekenhuis

Roeselaere, , Belgium

Clinique universitaire de Mont Godinne

Yvoir, , Belgium

Countries

Belgium

Other Identifiers

HYDRIC

Identifier Type: -

Identifier Source: org_study_id