R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT00504491

Last Updated: 2011-12-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2012-06-30

Brief Summary

Since there is no standard rescue therapy for refractory CLL or relapsed to the purine analogous, our target is to carry out a rescue therapy combining several chemotherapy agents (CHOP) adding the synergistic effect of Rituximab in order to act against tumour-like CLL forms, with assessable size lymph nodes. Afterwards, based in other studies, we shall study the role of Alemtuzumab as drug for consolidation or improvement of responses obtained with the initial therapy (CHOP-R), acting by "cleaning" from peripheral blood and bone marrow the CLL lymphocytes that may have had remain as residual after chemotherapy induction therapy. More precisely, the addition of Alemtuzumab as maintenance treatment would increase the complete responses with negative residual disease number and may prolong the duration of the response. For this, it is necessary to have not only an adequate and rigorous clinical follow-up but also biological, i.e. being able to analyze minimal residual disease by molecular biology techniques. This is the reason of writing this phase II clinical trial protocol.

Detailed Description

OBJECTIVES

The objectives of this clinical trial are the following:

• Main objective of the study: Overall response rate obtained after R-CHOP regime followed by Alemtuzumab consolidation as second line therapy
• Secondary objectives

• Determine the molecular complete response rate after R-CHOP regimen
• Determine the efficacy of Alemtuzumab in response improvement after R-CHOP regimen: conversion of PR to CR and of MRD+ to MRD-.
• Applicability (toxicity profile) of Alemtuzumab consolidation therapy.
• As additional objectives will be considered:

1. Prognostic value of several biological variables (ZAP-70 and cytogenetics) having influence on the response

2. Response duration

3. Progression free survival

4. Overall survival

Conditions

Chronic Lymphocytic Leukaemia; Patients Resistant to a Purine Analogous; Patients Relapsed With Purines Therapy

Keywords

Rituximab-CHOP; Alemtuzumab; Chronic lymphocytic leukaemia

Study Design

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

Study Groups

1

Four Rituximab - CHOP courses will be given The courses will be given every 21 days Drug Dose Day Rituximab (Mabthera) 500mg/m2 1(*) (**) Cyclophosphamide 750mg/m2 1 Adriamycin 50mg/m2 1 Vincristine 1,4 mg/m2 1 Prednisone 60mg/m2 1 to 5

(**) 1st course, 375 mg/m2 (*) If lymphocyte count is > 30 X 10 9/l, dose will be split up in two, which will be given in days 0 and 1

Group Type: EXPERIMENTAL

Rituximab-CHOP-Alemtuzumab

Intervention Type: DRUG

Four Rituximab - CHOP courses will be given The courses will be given every 21 days

Interventions

Rituximab-CHOP-Alemtuzumab

Four Rituximab - CHOP courses will be given The courses will be given every 21 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient's written informed consent before initiation of any specific procedure related with the study.

2. Age ≥ 18 years and ≤ 70 years

3. (ECOG) ≤ 2

4. Patients suffering from chronic lymphocyte leukaemia according to the established diagnostic criteria (Addendum A).

5. Active CLL defined by the presence of one or more of the following criteria:

• Related symptoms: weight loss >10% in the 6 previous months, or fever >38ºC for 2 weeks with no evidence of infections, or extreme fatigue, or night sweats with no evidence of infection.
• 5.2.Enlarged lymph nodes or giant node clusters (>10 cm in diameter) or progressive growth lymph nodes.
• 5.3.Giant splenomegaly (> 6 cm under ribs border) or progressive splenomegaly.
• 5.4.Progressive lymphocytosis (>50% increase in a period of 2 months) or lymphocyte duplication time (expected) < 6 months
• 5.5.Proof of progressive bone marrow failure evidenced by development or worsening of anaemia and/or thrombopenia.

6. Patients previously treated in first line with purine analogous and showing:

• Treatment failure (stable disease or progression)
• Relapse within three years of therapy.

7. Agreement to use a high efficacy contraception method throughout all study period.

Exclusion Criteria

1. Age > 70 years

2. Patients having received more than one therapy line

3. Patients that had not received previously purine analogous therapy.

4. CLL patients in transformation to more aggressive cytologic or pathologic forms (Pro-lymphocytic leukaemia large cell lymphoma, Hodgkin's lymphoma)

5. Hypersensitivity shown as anaphylactic reaction to any of the DRUGS used in the trial.

6. Patients with severe heart, lung, neurological, psychiatric or metabolic diseases not due to CLL

7. Patients under systemic and continued steroid therapy.

8. Impairment of renal function (Creatinine > 2 times the upper limit of normal) non-attributable to CLL.

9. Patients suffering anaemia or thrombocytopenia of autoimmune origin as well as those with a positive Coombs test

10. Impairment of liver function (Bilirubin, ASAT/ALAT or Gamma-GT > 2 times upper limit of normal) non attributable to CLL

11. Patients with active severe infectious disease

12. Patients suffering another malignancy (with the exception of focalized skin carcinoma)

13. Patients with positive serum tests for HBsAg or CHV

14. Patients with history of HIV or other severe immune depression conditions.

15. Pregnant or breast feeding women

16. Patients unable to attend the controls under outpatient regimen

17. Patients previously treated with alemtuzumab

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Francesc Bosch, MD

UNKNOWN

Sponsor Role: collaborator

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

OTHER

Sponsor Role: collaborator

Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

CABYC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesc Bosch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

Hospital de Son Dureta

Palma de Mallorca, Balearic Islands, Spain

ICO Badalona

Badalona, Barcelona, Spain

Hospital del Mar

Barcelona, Barcelona, Spain

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Hospital Valle de Hebron

Barcelona, Barcelona, Spain

ICO Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Althaia

Manresa, Barcelona, Spain

Corporacion Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Hospital de Basurto

Bilbao, Bilbao, Spain

Hospital Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Clinic i Provincial.

Barcelona, Catalonia, Spain

ICO Gerona

Girona, Girona, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Gran Canaria, Spain

Hospital Virgen de las Nieves

Granada, Granada, Spain

Hospital Arnau de Vilanova

Lleida, Lleida, Spain

Hospital La Princesa

Madrid, Madrid, Spain

Hospital Gregorio Marañon

Madrid, Madrid, Spain

M.D.Anderson Internacional

Madrid, Madrid, Spain

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Hospital 12 de octubre

Madrid, Madrid, Spain

Hospital Morales Meseguer

Murcia, Murcia, Spain

Hospital Clinico de Salamanca

Salamanca, Salamanca, Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, Santiago de Compostela, Spain

Hospital Virgen del Rocio

Seville, Sevilla, Spain

Hospital Joan XXIII

Tarragona, Tarragona, Spain

Hospital Francisco de Borja

Gandia, Valencia, Spain

Hospital La Fe

Valencia, Valencia, Spain

Hospital Clinico de Valencia

Valencia, Valencia, Spain

Hospital Doctor Peset

Valencia, Valencia, Spain

Hospital General de Valencia

Valencia, Valencia, Spain

Hospital Miguel Servet

Zaragoza, Zaragoza, Spain

Countries

Spain

Other Identifiers

2007-003097-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GELLC-2

Identifier Type: -

Identifier Source: org_study_id