R-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by European Institute of Oncology
Sponsor:
Information provided by (Responsible Party):
European Institute of Oncology
ClinicalTrials.gov Identifier:
NCT01446900
First received: June 15, 2011
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

The objective of this study is to confirm the efficacy of the association of R-2cda in patients affected by Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response.


Condition Intervention Phase
Chronic Lymphocytic Leukaemia
Small Lymphocytic Lymphoma
Drug: Rituximab
Drug: Cladribine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by European Institute of Oncology:

Primary Outcome Measures:
  • Response to treatment [ Time Frame: at month 17 ] [ Designated as safety issue: No ]
    response will be evaluated according to Hallek criteria and definitions


Secondary Outcome Measures:
  • Duration of response [ Time Frame: Every 6 months in the first year of follow-up and every 12 months afterwards until disease progression ] [ Designated as safety issue: No ]
    Duration of response Every 6 months in the first year of follow-up and every 12 months since second year until PD


Estimated Enrollment: 57
Study Start Date: January 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab cladribine Drug: Rituximab
375mg/mq, IV on day 1 of each 28 day cycle for 4 cycles. 375 mg/mq IV every 2 months for a total of 8 administrations as additional infusions for patients, who achieve a partial response or complete response after the therapy with R- 2-CdA.
Other Name: Mabthera
Drug: Cladribine
0,1 mg/Kg, SC from day 1 to day 5 of each 28 day cycle for 4 cycles.
Other Name: Litak

Detailed Description:

Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder characterized by the progressive accumulation of monoclonal peripheral B cells in bone marrow, peripheral blood and lymphoid tissues. Median survival is about 10 years. It is now clear that front line therapy for a patient with CLL requiring treatment should be the association of purine analogue and rituximab with or without cyclophosphamide. Concerning the choice of the purine analogue, similar results have been obtained by using cladribine instead of fludarabine. Although cladribine is less commonly used, the direct comparison between the two analogues for what concerns efficacy and toxicity, has confirmed the same profile of the two drugs. Encouraging results have been obtained using the monoclonal antibody in association with the purine analogue.

The utilization of rituximab as a maintenance therapy could improve the response in cases of persistence of minimal residual disease as well as delay the insurgence of relapses thus increasing the DFS.

The objective of this study is to confirm the efficacy of the association of R-2cda and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response. The results of this study will be compared with existing clinical results from a group of 42 pts already treated as standard with R-2cda without additional rituximab infusions.

Patients enrolled in the study will receive 4 cycles of R-2-CdA therapy. Patients, who achieve a partial response or complete response after the therapy with R- 2-CdA, will prolong therapy with Rituximab. The therapy will begin 3 months after the end of the induction therapy and patients will receive one administration every 2 months for a total of 8 administrations.

  Eligibility

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

Inclusion Criteria:

  • Aged ≥ 18 years
  • Patients affected by CLL / SLL
  • Presence of active disease defined as the presence of one of the following:

Disease related symptoms (weight loss >10% in the last 6 months, fever >38° C for 2 weeks without evidence of infection, or marked asthenia, or profuse sweating without evidence of infection) Massive nodes (at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Massive (at least 6 cm below left costal margin) or progressive or symptomatic splenomegaly Progressive lymphocytosis (increased >50% in 2 months) or lymphocyte doubling time < 6 months Evidence of progressive bone marrow insufficiency seen as evidence of or worsening of anemia and or thrombocytopenia Autoimmune anemia and or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy

Exclusion Criteria:

  • Age < 18 years
  • Patients with cardiac, pulmonary, neurological, psychiatric or serious metabolic conditions not related to CLL / SLL
  • Altered hepatic function (bilirubin, GOT, GPT, or gammaGT > 2 times upper limit of normal) not attributable to CLL / SLL
  • Altered renal function (creatinine > 1,5 times upper limit of normal)
  • Patients with serious active infections
  • Pregnancy and/ or breastfeeding
  • Patients with positive serology for HBSAG or HBCAB without evaluation by a hepatologist
  • Patients with positive serology for HIV
  • Life expectancy of less than 12 months
  • Not taking any other experimental drugs
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cladribine (2CdA).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446900

Contacts
Contact: Giovanni Martinelli, MD +390257489538 giovanni.martinelli@ieo.it

Locations
Italy
European Institute of Oncology Recruiting
Milan, Italy
Contact: giovanni martinelli         
Principal Investigator: Giovanni Martinelli, MD         
Sponsors and Collaborators
European Institute of Oncology
Investigators
Study Chair: Giovanni Martinelli, MD European Institute of Oncology
  More Information

Publications:
Responsible Party: European Institute of Oncology
ClinicalTrials.gov Identifier: NCT01446900     History of Changes
Other Study ID Numbers: IEO S523/110, 2010-018519-14
Study First Received: June 15, 2011
Last Updated: June 17, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by European Institute of Oncology:
Rituximab
Cladribine
Chronic Lymphocytic Leukaemia
Small Lymphocytic Lymphoma

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Cladribine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 01, 2014