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

Chronic Lymphocytic Leukemia Clinical Trial

— LLCRlowdoz  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01521689
• Other study ID #: LLCR lowdoz / IPC 2009-004
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 22, 2011
• Last updated: March 19, 2015
• Start date: December 2011
• Est. completion date: June 2015

Study information

• Verified date: March 2015
• Source: Institut Paoli-Calmettes
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Rituximab
Low doses of sub cutaneaous rituximab

Locations

Country	Name	City	State
France	Institut Paoli Calmettes	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Institut Paoli-Calmettes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Residual disease	- 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	up to 3 month after the end of treatment	No
Secondary	overall survival	time between inclusion and death	From date of inclusion until date of death, assessed up to 10 years	No
Secondary	Adverse events	Number and description of adverse events recorded according to the CTC-AE V4	up to 3 months	Yes
Secondary	-Quality of life	-Quality of life study by QLQ-C30	up to 3 months after the end of treatment	No
Secondary	Immune functions	NK, monocytes, CD8, and CD 20 expression on leucemic cells or B cells	up to 3 months after the end of treatment	No
Secondary	- Progression free survival	Time between inclusion and progression	up to time of progression assessed up to 10 years	No
Secondary	treatment free survival	time between end of treatment and restarting a new treatement	up to time of new treatment assessed up to 10 years	No

External Links

•   Web site of the sponsor