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

NCT01625741 | Terminated Phase 2

• 1 other identifier: HYDRIC
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 15

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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• rate of conversion into Minimal Residual Disease negativity

  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 Outcomes (3)

• toxicity of the consolidation treatment by rituximab

  from first administration of rituximab until end of follow-up period (= 12 months after the last rituximab administration)

• Pharmacokinetic/Pharmacodynamic correlation

  month 7

• quality of life study

  during 17 months

Study Arms (1)

rituximab

EXPERIMENTAL

4 monthly administrations of rituximab

Drug: Rituximab

Interventions

Rituximab DRUG

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

Also known as: Mabthera

rituximab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :
• 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
• 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:
• 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…)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (15)

ZNA Middelheim

Antwerp, 2020, Belgium

Location

Clinique Sud Luxembourg

Arlon, 6700, Belgium

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Clinique Saint Jean

Brussels, 1000, Belgium

Location

ULB Erasme

Brussels, 1070, Belgium

Location

Cliniques universitaires Saint Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Hôpital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

KUL Gasthuisberg

Leuven, 3000, Belgium

Location

CHU ULg Sart Tilman

Liège, 4000, Belgium

Location

CHR Clinique Saint Joseph

Mons, 7000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

Heilig-Hartziekenhuis

Roeselaere, 8800, Belgium

Location

Clinique universitaire de Mont Godinne

Yvoir, 5530, Belgium

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eric Van Den Neste, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 21, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: September 29, 2015

Record last verified: 2015-09

Locations

BE (15)