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| ID | Type | Description | Link |
|---|---|---|---|
| CHRUT-LLC-2007-SA | Other Identifier | CHU Tours | |
| CHRUT-PHRN05-CD | Other Identifier | CHU Tours | |
| INCA-RECF0497 | Other Identifier | INCA | |
| 2007-001015-28 | EudraCT Number |
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| Name | Class |
|---|---|
| Roche Pharma AG | INDUSTRY |
| French Innovative Leukemia Organisation | OTHER |
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RATIONALE: Classical chemotherapy does not cure advanced chronic lymphocytic leukemia (CLL) despite new drugs. Rituximab is a monoclonal antibody directed against CD20 surface antigen on B lymphocytes and leads to apoptosis of CD20 positive B lymphocytes. The highest response rate yet published in the treatment of first-line CLL has been obtained by the association of fludarabine, cyclophosphamide and rituximab (FCR). Now, the question is whether this response can be improved, as some trials showed that eradication of minimal residual disease (MRD) in CLL is associated with a longer treatment-free and overall survival. Maintenance therapy using rituximab has been recently approved as a means of prolonging remission in patients with indolent non Hodgkin's lymphoma. Maintenance therapy with rituximab could be of interest in treatment of MRD in CLL and prolonging remission and survival times.
PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (>65 years) patients who respond to induction immunochemotherapy with FCR.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Randomization is stratified according to response to induction therapy (complete response [CR] vs partial response [PR]), IGHV mutational status, and 11q deletion.
Patients receive rituximab IV on days 1 and 14 of courses 1-2 and on day 1 of courses 3 and 4. Patients also receive oral fludarabine and oral cyclophosphamide once daily on days 2-4 of course 1 and on days 1-3 of courses 2-4. Courses are administered every 28 days. Patients achieving CR or PR are randomized 1:1 to maintenance arm or observation arm.
After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Observation | No Intervention | Observation every 8 weeks during 2 years | |
| rituximab arm | Experimental | rituximab :500 mg/m² every 8 weeks during 2 years |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Biological | rituximab :500 mg/m² every 8 weeks during 2 years |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival | Progression-free survival is defined as the time from randomization to the first occurrence of disease progression, relapse or death from any cause; using iwCLL criteria | randomization until disease progression or death |
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival | Event-free survival is defined as the time from randomization to the occurrence of one of the following events, whichever occurs first: disease progression or relapse, death from any cause, initiation of any new anti-CLL therapy, and secondary malignancy | randomization until disease progression, death, new CLL treatment, and secondary cancer |
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Inclusion criteria
Exclusion criteria
Inclusion criteria at randomization
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| Name | Affiliation | Role |
|---|---|---|
| Caroline Dartigeas, MD | Hématologie et Thérapie Cellulaire Hôpital Bretonneau CHU Tours FRANCE | Principal Investigator |
| Eric VAN DEN NESTE, MD PhD | Département d'hématologie Cliniques Universitaires Saint Luc BRUSSELS BELGIUM | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| French Innovative leukemia Organization | Tours | 37044 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29275118 | Derived | Dartigeas C, Van Den Neste E, Leger J, Maisonneuve H, Berthou C, Dilhuydy MS, De Guibert S, Lepretre S, Bene MC, Nguyen-Khac F, Letestu R, Cymbalista F, Rodon P, Aurran-Schleinitz T, Vilque JP, Tournilhac O, Mahe B, Laribi K, Michallet AS, Delmer A, Feugier P, Levy V, Delepine R, Colombat P, Leblond V; CLL 2007 SA investigators; French Innovative Leukemia Organization (FILO). Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study. Lancet Haematol. 2018 Feb;5(2):e82-e94. doi: 10.1016/S2352-3026(17)30235-1. Epub 2017 Dec 20. |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Disease-free survival | Disease-free survival is defined as the time from first documented CR to relapse | first documented CR until relapse |
| Overall survival | Overall survival is defined as the time from randomization to death from any cause | randomization until death |
| Time to next treatment | Time to next treatment is defined as the time from randomization to initiation of a new CLL-related treatment | randomization until new CLL treatment |
| Overall response rate | Overall response rate is defined by the percentage of participants with an overall response; CR or PR according to NCI criteria and CR, CRi or PR according to iwCLL | baseline up to approximately 66 months |
| Phenotypic response rate | Phenotypic response rate is defined by the percentage of participants with minimal residual disease negativity as measured by six-colour flow cytometry with a sensitivity of 0.7 x 10-5. MRD is considered as undetectable when the positivity criteria, defined as the presence of at least 20 CLL cells, is not reached | randomization up to approximately 60 months |
| Rates of treatment-related adverse events | Rate of treatment-related adverse events (plus adverse events of particular interest) is defined as the percentage of participants with adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and version 2.0. for hematological toxicity | safety since baseline |
| Pharmacokinetics of rituximab | Pharmacokinetics of rituximab during induction and rituximab maintenance | baseline up to approximately 36 months |
| Quality of life | Change from baseline in EORTC Quality of Life Questionnaire Core 30 | baseline up to approximately 30 months |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |