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

NCT ID: NCT01446900

Last Updated: 2018-01-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2017-12-31

Brief Summary

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.

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.

Conditions

Chronic Lymphocytic Leukaemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab cladribine

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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.

Cladribine

Intervention Type: DRUG

0,1 mg/Kg, SC from day 1 to day 5 of each 28 day cycle for 4 cycles.

Interventions

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.

Intervention Type: DRUG

Cladribine

0,1 mg/Kg, SC from day 1 to day 5 of each 28 day cycle for 4 cycles.

Intervention Type: DRUG

Other Intervention Names

Mabthera; Litak

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giovanni Martinelli, MD

Role: STUDY_CHAIR

European Institute of Oncology

Locations

European Institute of Oncology

Milan, , Italy

Countries

Italy

References

Bertazzoni P, Rabascio C, Gigli F, Calabrese L, Radice D, Calleri A, Gregato G, Negri M, Liptrott SJ, Bassi S, Nassi L, Sammassimo S, Laszlo D, Preda L, Pruneri G, Orlando L, Martinelli G. Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients. Leuk Lymphoma. 2010 Aug;51(8):1485-93. doi: 10.3109/10428194.2010.495799.

Reference Type: BACKGROUND

PMID: 20578816 (View on PubMed)

Del Poeta G, Del Principe MI, Buccisano F, Maurillo L, Capelli G, Luciano F, Perrotti AP, Degan M, Venditti A, de Fabritiis P, Gattei V, Amadori S. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer. 2008 Jan 1;112(1):119-28. doi: 10.1002/cncr.23144.

Reference Type: BACKGROUND

PMID: 17999417 (View on PubMed)

Other Identifiers

2010-018519-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IEO S523/110

Identifier Type: -

Identifier Source: org_study_id