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

This study is currently recruiting participants.
Verified March 2013 by Institut Paoli-Calmettes
Sponsor:
Information provided by (Responsible Party):
Institut Paoli-Calmettes
ClinicalTrials.gov Identifier:
NCT01521689
First received: December 22, 2011
Last updated: March 19, 2013
Last verified: March 2013
History of Changes
  Purpose

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 Intervention Phase
Chronic Lymphocytic Leukemia
 Drug: Rituximab
 Phase 2

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

Resource links provided by NLM:

Drug Information available for: Rituximab
U.S. FDA Resources

Further study details as provided by Institut Paoli-Calmettes:

Primary Outcome Measures:
  • Residual disease [ Time Frame: up to 3 month after the end of treatment ] [ Designated as safety issue: No ]
    - 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:
  • overall survival [ Time Frame: From date of inclusion until date of death, assessed up to 10 years ] [ Designated as safety issue: No ]
    time between inclusion and death

  • Adverse events [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
    Number and description of adverse events recorded according to the CTC-AE V4

  • -Quality of life [ Time Frame: up to 3 months after the end of treatment ] [ Designated as safety issue: No ]
    -Quality of life study by QLQ-C30

  • Immune functions [ Time Frame: up to 3 months after the end of treatment ] [ Designated as safety issue: No ]
    NK, monocytes, CD8, and CD 20 expression on leucemic cells or B cells

  • - Progression free survival [ Time Frame: up to time of progression assessed up to 10 years ] [ Designated as safety issue: No ]
    Time between inclusion and progression

  • treatment free survival [ Time Frame: up to time of new treatment assessed up to 10 years ] [ Designated as safety issue: No ]
    time between end of treatment and restarting a new treatement


Estimated Enrollment: 35
Study Start Date: December 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Consolidation treatment with sub cutaneaous low doses of Rituximab
 Drug: Rituximab
Low doses of sub cutaneaous rituximab
Other Name: Rituximab

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01521689

Contacts
Contact: Dominique GENRE, MD 33 4 91 22 37 78 bec@ipc.unicancer.fr
Contact: Agnès BOYER CHAMMARD, MD 33 4 91 22 37 78 bec@ipc.unicancer.fr

Locations
France
Institut Paoli Calmettes Recruiting
Marseille, France, 13009
Contact: Thérèse AURRAN, MD     33491223778     bec@ipc.unicancer.fr    
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
Principal Investigator: Thérèse AURRAN, MD Institut Paoli-Calmettes
  More Information

Additional Information:
Web site of the sponsor  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT01521689     History of Changes
Other Study ID Numbers: LLCR lowdoz / IPC 2009-004
Study First Received: December 22, 2011
Last Updated: March 19, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Institut Paoli-Calmettes:
MRD negative CR

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
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 16, 2013