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Tolerance and Efficacy of Subcutanous Low Doses Rituximab for CLL Consolidation Treatment (LLCRlowdoz)

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: NCT01521689
Recruitment Status : Unknown
Verified March 2015 by Institut Paoli-Calmettes.
Recruitment status was:  Active, not recruiting
First Posted : January 31, 2012
Last Update Posted : March 20, 2015
Information provided by (Responsible Party):
Institut Paoli-Calmettes

Brief Summary:

Chronic Lymphocytic Leukemia (CLL) is still an incurable disease. However recent advances have established correlation between the quality of the response (in particular achievement of negativity of minimal residual disease (MRD) and progression free and overall survival. That is why MRD negative complete remission (CR) is the current goal in CLL treatment.

The association of Rituximab fludarabine cyclophosphamide leads to the best response rate with 52 to 72% CR in "medically" fit untreated CLL patients. MRD results in this setting are still preliminary and around 50%. However many other situations (unfit, elderly, relapse, haematological toxicity leading to early interruption of treatment…) are associated with much lower response rate that would be improved by consolidation treatment.

Monoclonal antibodies are the treatment of choice for consolidation because of sparing marrow and targeting CLL cells. Alemtuzumab has been used for this purpose and results confirm improvement of CR and MRD negative responses but alemtuzumab induced immunodeficiency lead to unacceptable infectious complications. Rituximab monotherapy induces low response rate at standard dose regimen. This is at least partially due to shaving of CD20, mechanism by which CD20 is lost from the leukemic cells but these cells are not cleared. Using low doses of rituximab reduced shaving and allowed CLL cells clearance by the mononuclear phagocytic system. Such low doses of rituximab can be administered subcutaneously.

The investigators then propose subcutaneous low dose rituximab in consolidation to CLL patients responding after induction but having not achieved MRD negative CR.

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

Detailed Description:

Objective(s) of the clinical study

Main objective:

- To improve the minimal residual disease (MRD) negative complete response (CR) rate after consolidation using subcutaneous low dose of rituximab

Secondary objectives:

  • Progression free survival, treatment free survival, overall survival,
  • MRD follow-up,
  • Safety
  • Medico-economic study
  • Quality of life study
  • Immune functions study (ancillary study)

Main assessment criteria:

MRD negative CR rate, established by peripheral blood 4colour flow cytometry according to international consensus on CLL MRD study, at the end of the consolidation treatment.

Experimental plan:

Inclusion of patients after the evaluation of response to induction treatment according to NCI-ICLLWG criteria and MRD analysis (2 to 3 months after induction completion): patients having not achieved MRD negative CR.

Consolidation treatment by subcutaneous rituximab given at 20 mg/m²/d thrice weekly during 12 weeks.

Evaluation of the response 3 months after completion of the consolidation treatment.

Subjects number: 35 patients will be needed to accept the hypothesis of an augmentation of CR with negative MRD >=40%, excluding the hypothesis that this rate is < 20%. This ensure us an alpha risk at 5% with a 80% power, taking into account that non evaluable patients will be < 5%.

Brief description of the ancillary study:

Immune functions study before and after consolidation treatment by rituximab

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Tolerance and Efficacy of Subcutanous Low Doses Rituximab Given as Consolidation Treatment to Chronic Lymphocytic Leukaemia (CLL) Patients Responding to Induction Therapy
Study Start Date : December 2011
Estimated Primary Completion Date : June 2015
Estimated Study Completion Date : June 2015

Arm Intervention/treatment
Experimental: Rituximab
Consolidation treatment with sub cutaneaous low doses of Rituximab
Drug: Rituximab
Low doses of sub cutaneaous rituximab

Primary Outcome Measures :
  1. Residual disease [ Time Frame: up to 3 month after the end of treatment ]
    - minimal residual disease (MRD) negative complete response (CR) rate after consolidation using subcutaneous low dose of rituximab, from randomisation up to 3 month after the end of treatment

Secondary Outcome Measures :
  1. overall survival [ Time Frame: From date of inclusion until date of death, assessed up to 10 years ]
    time between inclusion and death

  2. Adverse events [ Time Frame: up to 3 months ]
    Number and description of adverse events recorded according to the CTC-AE V4

  3. -Quality of life [ Time Frame: up to 3 months after the end of treatment ]
    -Quality of life study by QLQ-C30

  4. Immune functions [ Time Frame: up to 3 months after the end of treatment ]
    NK, monocytes, CD8, and CD 20 expression on leucemic cells or B cells

  5. - Progression free survival [ Time Frame: up to time of progression assessed up to 10 years ]
    Time between inclusion and progression

  6. treatment free survival [ Time Frame: up to time of new treatment assessed up to 10 years ]
    time between end of treatment and restarting a new treatement

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • CLL (Matutes 4 or 5) in CR after induction treatment with negative MRD or PR
  • age>18
  • performance status<=2
  • signed informed consent

Exclusion Criteria:

  • cytopenia
  • other malignant affection
  • HIV or HBV positive
  • steroids treatment
  • richter syndrome
  • pregnant or breastfeeding women

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): NCT01521689

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Institut Paoli Calmettes
Marseille, France, 13009
Sponsors and Collaborators
Institut Paoli-Calmettes
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Principal Investigator: Thérèse AURRAN, MD Institut Paoli-Calmettes

Additional Information:
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Responsible Party: Institut Paoli-Calmettes Identifier: NCT01521689     History of Changes
Other Study ID Numbers: LLCR lowdoz / IPC 2009-004
First Posted: January 31, 2012    Key Record Dates
Last Update Posted: March 20, 2015
Last Verified: March 2015
Keywords provided by Institut Paoli-Calmettes:
MRD negative CR
Additional relevant MeSH terms:
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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, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents