Clinical trial NCT00504491: R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia
Official title: Rescue Treatment With Rituximab-CHOP Therapy and Alemtuzumab (R-CHOP-A) in Refractory or Recidivant Patients With Chronic Lymphocytic Leukemia After Purine-analogous Treatment
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukaemia
Patients Resistant to a Purine Analogous
Patients Relapsed With Purines Therapy
Keywords: Rituximab-CHOP
Alemtuzumab
Chronic lymphocytic leukaemia
Lead sponsor: CABYC
Sponsor class: INDUSTRY
Collaborators: name: Francesc Bosch, MD
name: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
name: Fundacion Clinic per a la Recerca Biomédica
name: Bayer
name: Genzyme, a Sanofi Company
First posted: 2007-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Response rate obtained after R-CHOP regimen followed by consolidation therapy with Alemtuzumab, as second line therapy. Haematological and non haematological toxicity will be graded in accordance with the WHO system
timeFrame: 57 months
Secondary outcomes:
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: ICO Badalona
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO Bellvitge
state: Barcelona
city: Manresa
country: Spain
facility: Althaia
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacion Sanitaria Parc Tauli
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial.
state: Cataluña
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Gran Canaria
city: Palma de Mallorca
country: Spain
facility: Hospital de Son Dureta
state: Islas Baleares
city: Gandia
country: Spain
facility: Hospital Francisco de Borja
state: Valencia
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Valle de Hebron
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Girona
country: Spain
facility: ICO Gerona
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: M.D.Anderson Internacional
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de octubre
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Salamanca
country: Spain
facility: Hospital Clinico de Salamanca
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
city: Valencia
country: Spain
facility: Hospital Doctor Peset
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Francesc Bosch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: