R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

This study has been withdrawn prior to enrollment.
(IMP new owner decision)
Sponsor:
Collaborators:
Francesc Bosch, MD
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Fundacion Clinic per a la Recerca Biomédica
Bayer
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
CABYC
ClinicalTrials.gov Identifier:
NCT00504491
First received: July 19, 2007
Last updated: December 28, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukaemia
Patients Resistant to a Purine Analogous
Patients Relapsed With Purines Therapy
Drug: Rituximab-CHOP-Alemtuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by CABYC:

Primary Outcome Measures:
  • 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 [ Time Frame: 57 months ]

Enrollment: 0
Study Start Date: July 2007
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

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

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00504491

Locations
Spain
ICO Badalona
Badalona, Barcelona, Spain, 08916
ICO Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Althaia
Manresa, Barcelona, Spain, 08243
Corporacion Sanitaria Parc Tauli
Sabadell, Barcelona, Spain, 08208
Hospital Clinic i Provincial.
Barcelona, Cataluña, Spain, 08036
Hospital Universitario de Canarias
La Laguna, Gran Canaria, Spain, 38320
Hospital de Son Dureta
Palma de Mallorca, Islas Baleares, Spain, 07014
Hospital Francisco de Borja
Gandia, Valencia, Spain, 46700
Hospital Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Valle de Hebron
Barcelona, Spain, 08035
Hospital del Mar
Barcelona, Spain, 08003
Hospital de Basurto
Bilbao, Spain, 48013
ICO Gerona
Girona, Spain, 17007
Hospital Virgen de las Nieves
Granada, Spain, 18014
Hospital Arnau de Vilanova
Lleida, Spain, 25198
M.D.Anderson Internacional
Madrid, Spain, 28033
Hospital Gregorio Marañon
Madrid, Spain, 28007
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital 12 de octubre
Madrid, Spain, 28041
Hospital La Princesa
Madrid, Spain, 28006
Hospital Morales Meseguer
Murcia, Spain, 30008
Hospital Clinico de Salamanca
Salamanca, Spain, 37007
Hospital Marques de Valdecilla
Santander, Spain, 39008
Hospital Clinico Universitario de Santiago
Santiago de Compostela, Spain, 36680
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Hospital Joan XXIII
Tarragona, Spain, 43005
Hospital Clinico de Valencia
Valencia, Spain, 46011
Hospital Doctor Peset
Valencia, Spain, 46017
Hospital La Fe
Valencia, Spain, 46009
Hospital General de Valencia
Valencia, Spain, 46018
Hospital Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
CABYC
Francesc Bosch, MD
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Fundacion Clinic per a la Recerca Biomédica
Bayer
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Francesc Bosch, MD, PhD Hospital Clinic de Barcelona
  More Information

No publications provided

Responsible Party: CABYC
ClinicalTrials.gov Identifier: NCT00504491     History of Changes
Other Study ID Numbers: GELLC-2, 2007-003097-26
Study First Received: July 19, 2007
Last Updated: December 28, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by CABYC:
Rituximab-CHOP
Alemtuzumab
Chronic lymphocytic leukaemia

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

ClinicalTrials.gov processed this record on October 01, 2014