LLC-LENAR-08 A PHASE I/II STUDY LENALIDOMIDE-RITUXIMAB IN RELAPSE/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA
Author(s): ,
Adolfo De La Fuente
Affiliations:
Hematology,MD Anderson CC Madrid Spain,Madrid,Spain
,
Marcos Gonzalez
Affiliations:
Hematology,H. U. Salamanca,Salamanca,Spain
,
Pilar Giraldo
Affiliations:
Hematology,H. U. Miguel Servet,Zaragoza,Spain
,
F de la Cruz
Affiliations:
Hematology,H. U. Virgen del Rocio,Sevilla,Spain
,
Maria Jose Terol
Affiliations:
Hematology,H. U. Clinico de Valencia,Valencia,Spain
,
Jose Antonio Perez Simon
Affiliations:
Hematology,H. U. Virgen del Rocio,Sevilla,Spain
,
G Rodriguez
Affiliations:
Hematology,H. U. Reina Sofia Cordoba,Cordoba,Spain
,
Carlos Montalban
Affiliations:
Hematology,MD Anderson CC Madrid Spain,Madrid,Spain
,
Jose Francisco Toas
Affiliations:
Hematology,Bupa-SLA Madrid,Madrid,Spain
Raquel de Oña
Affiliations:
Hematology,MD Anderson CC Madrid Spain,Madrid,Spain
EHA Library. De La Fuente A. 06/12/15; 100471; P217 Disclosure(s): MD Anderson CC Madrid Spain
Hematology
Dr. Adolfo De La Fuente
Dr. Adolfo De La Fuente
Contributions
Abstract
Abstract: P217

Type: Poster Presentation

Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45

Location: Poster area (Hall C)

Background

Phase II studies showed  lenalidomide monotherapy is active in relapsed and refractory CLL. A synergistic activity between rituximab and lenalidomide against CLL has been suggested and a previous study has evaluated the combination of lenalidomide and rituximab in this population with encouraging results (J Clin Oncol, 2012,31: 584),  but the optimal dose and schedule for this combination remains unknown.



Aims

The endpoint in phase I of this study is to define the optimum dose of lenalidomide in combination with rituximab in R/R CLL patients. The endpoint in  phase II is to evaluate effectiveness and toxic profile of the resulted schedule.



Methods

We carried out a multicenter phase I/II study on R/R CLL patients, in the dose finding phase we started with a continuous lenalidomide daily dose of 2,5mg and rituximab (375mg/m2 cycle 1 and 500mg/m2 cycles 2-6/28 days) with cohorts of 3 patients (if no DLT move to a higher dose; if one DLT occurred in the cohort expand 3 more patients). In the second phase we evaluated efficacy (NCI WGC criteria), toxic profile (CTCAE v3.0 scale) OS and TTP with Kaplan Meier. Study registered in ClinicalTrials.gov:NCT01185262.

 



Results

We reported our completed Phase I/II study, 29pt from 7 Spanish sites were enrolled, 4 of them were screening failures because criteria not fulfilled, and 5 withdrew consent to participate before starting treatment. Median age 75 yr (45-86), male/female 11/9, ECOG 0/1/2: 7/12/1, median time from diagnosis 7.8 yr, median number of previous lines 2 (1-4) all but 2 pt had received fludarabine. In  phase I the MTD of lenalidomide was 15 mg. Effectiveness: In phase II ORR 7 pt (53%), all PR, estimated TTP 15.4 months, estimated OS 21.9 months. Toxicity: 34 SAE were reported, in 6 cases treatment was discontinued definitively (infection 4 pt, progressive multifocal leukoencephalopathy 1pt, amyotrophic lateral sclerosis 1pt). Grade 4 neutropenia was the main adverse event associated with the regimen.



Summary
In our experience 15 mg is the MTD of daily lenalidomide in combination with rituximab every 28 days in R/R CLL patients. The combination was effective and well tolerated with a 53% ORR and 21.9 months estimated OS.

Keyword(s): Chronic lymphocytic leukemia, Phase I/II, Salvage therapy

Session topic: Chronic lymphocytic leukemia - Clinical 1
Abstract: P217

Type: Poster Presentation

Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45

Location: Poster area (Hall C)

Background

Phase II studies showed  lenalidomide monotherapy is active in relapsed and refractory CLL. A synergistic activity between rituximab and lenalidomide against CLL has been suggested and a previous study has evaluated the combination of lenalidomide and rituximab in this population with encouraging results (J Clin Oncol, 2012,31: 584),  but the optimal dose and schedule for this combination remains unknown.



Aims

The endpoint in phase I of this study is to define the optimum dose of lenalidomide in combination with rituximab in R/R CLL patients. The endpoint in  phase II is to evaluate effectiveness and toxic profile of the resulted schedule.



Methods

We carried out a multicenter phase I/II study on R/R CLL patients, in the dose finding phase we started with a continuous lenalidomide daily dose of 2,5mg and rituximab (375mg/m2 cycle 1 and 500mg/m2 cycles 2-6/28 days) with cohorts of 3 patients (if no DLT move to a higher dose; if one DLT occurred in the cohort expand 3 more patients). In the second phase we evaluated efficacy (NCI WGC criteria), toxic profile (CTCAE v3.0 scale) OS and TTP with Kaplan Meier. Study registered in ClinicalTrials.gov:NCT01185262.

 



Results

We reported our completed Phase I/II study, 29pt from 7 Spanish sites were enrolled, 4 of them were screening failures because criteria not fulfilled, and 5 withdrew consent to participate before starting treatment. Median age 75 yr (45-86), male/female 11/9, ECOG 0/1/2: 7/12/1, median time from diagnosis 7.8 yr, median number of previous lines 2 (1-4) all but 2 pt had received fludarabine. In  phase I the MTD of lenalidomide was 15 mg. Effectiveness: In phase II ORR 7 pt (53%), all PR, estimated TTP 15.4 months, estimated OS 21.9 months. Toxicity: 34 SAE were reported, in 6 cases treatment was discontinued definitively (infection 4 pt, progressive multifocal leukoencephalopathy 1pt, amyotrophic lateral sclerosis 1pt). Grade 4 neutropenia was the main adverse event associated with the regimen.



Summary
In our experience 15 mg is the MTD of daily lenalidomide in combination with rituximab every 28 days in R/R CLL patients. The combination was effective and well tolerated with a 53% ORR and 21.9 months estimated OS.

Keyword(s): Chronic lymphocytic leukemia, Phase I/II, Salvage therapy

Session topic: Chronic lymphocytic leukemia - Clinical 1

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