search
Back to results

R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia (R-CHOP)

Primary Purpose

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

Status
Withdrawn
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Rituximab-CHOP-Alemtuzumab
Sponsored by
CABYC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukaemia focused on measuring Rituximab-CHOP, Alemtuzumab, Chronic lymphocytic leukaemia

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ICO Badalona
  • ICO Bellvitge
  • Althaia
  • Corporacion Sanitaria Parc Tauli
  • Hospital Clinic i Provincial.
  • Hospital Universitario de Canarias
  • Hospital de Son Dureta
  • Hospital Francisco de Borja
  • Hospital del Mar
  • Hospital Santa Creu i Sant Pau
  • Hospital Valle de Hebron
  • Hospital de Basurto
  • ICO Gerona
  • Hospital Virgen de las Nieves
  • Hospital Arnau de Vilanova
  • Hospital La Princesa
  • Hospital Gregorio Marañon
  • M.D.Anderson Internacional
  • Hospital Ramón y Cajal
  • Hospital Clínico San Carlos
  • Hospital 12 de octubre
  • Hospital Morales Meseguer
  • Hospital Clinico de Salamanca
  • Hospital Marques de Valdecilla
  • Hospital Clinico Universitario de Santiago
  • Hospital Virgen del Rocio
  • Hospital Joan XXIII
  • Hospital La Fe
  • Hospital Clinico de Valencia
  • Hospital Doctor Peset
  • Hospital General de Valencia
  • Hospital Miguel Servet

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

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

Outcomes

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

Secondary Outcome Measures

Full Information

First Posted
July 19, 2007
Last Updated
December 28, 2011
Sponsor
CABYC
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
search

1. Study Identification

Unique Protocol Identification Number
NCT00504491
Brief Title
R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia
Acronym
R-CHOP
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

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Withdrawn
Why Stopped
IMP new owner decision
Study Start Date
July 2007 (undefined)
Primary Completion Date
January 2012 (Anticipated)
Study Completion Date
June 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CABYC
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: Prognostic value of several biological variables (ZAP-70 and cytogenetics) having influence on the response Response duration Progression free survival Overall survival

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukaemia, Patients Resistant to a Purine Analogous, Patients Relapsed With Purines Therapy
Keywords
Rituximab-CHOP, Alemtuzumab, Chronic lymphocytic leukaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab-CHOP-Alemtuzumab
Intervention Description
Four Rituximab - CHOP courses will be given The courses will be given every 21 days
Primary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient's written informed consent before initiation of any specific procedure related with the study. Age ≥ 18 years and ≤ 70 years (ECOG) ≤ 2 Patients suffering from chronic lymphocyte leukaemia according to the established diagnostic criteria (Addendum A). 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. Patients previously treated in first line with purine analogous and showing: Treatment failure (stable disease or progression) Relapse within three years of therapy. Agreement to use a high efficacy contraception method throughout all study period. Exclusion Criteria: Age > 70 years Patients having received more than one therapy line Patients that had not received previously purine analogous therapy. CLL patients in transformation to more aggressive cytologic or pathologic forms (Pro-lymphocytic leukaemia large cell lymphoma, Hodgkin's lymphoma) Hypersensitivity shown as anaphylactic reaction to any of the DRUGS used in the trial. Patients with severe heart, lung, neurological, psychiatric or metabolic diseases not due to CLL Patients under systemic and continued steroid therapy. Impairment of renal function (Creatinine > 2 times the upper limit of normal) non-attributable to CLL. Patients suffering anaemia or thrombocytopenia of autoimmune origin as well as those with a positive Coombs test Impairment of liver function (Bilirubin, ASAT/ALAT or Gamma-GT > 2 times upper limit of normal) non attributable to CLL Patients with active severe infectious disease Patients suffering another malignancy (with the exception of focalized skin carcinoma) Patients with positive serum tests for HBsAg or CHV Patients with history of HIV or other severe immune depression conditions. Pregnant or breast feeding women Patients unable to attend the controls under outpatient regimen Patients previously treated with alemtuzumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesc Bosch, MD, PhD
Organizational Affiliation
Hospital Clinic of Barcelona
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICO Badalona
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
ICO Bellvitge
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Althaia
City
Manresa
State/Province
Barcelona
ZIP/Postal Code
08243
Country
Spain
Facility Name
Corporacion Sanitaria Parc Tauli
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Clinic i Provincial.
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
La Laguna
State/Province
Gran Canaria
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hospital de Son Dureta
City
Palma de Mallorca
State/Province
Islas Baleares
ZIP/Postal Code
07014
Country
Spain
Facility Name
Hospital Francisco de Borja
City
Gandia
State/Province
Valencia
ZIP/Postal Code
46700
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Valle de Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital de Basurto
City
Bilbao
ZIP/Postal Code
48013
Country
Spain
Facility Name
ICO Gerona
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Virgen de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Hospital Arnau de Vilanova
City
Lleida
ZIP/Postal Code
25198
Country
Spain
Facility Name
Hospital La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
M.D.Anderson Internacional
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital 12 de octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Morales Meseguer
City
Murcia
ZIP/Postal Code
30008
Country
Spain
Facility Name
Hospital Clinico de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Marques de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Clinico Universitario de Santiago
City
Santiago de Compostela
ZIP/Postal Code
36680
Country
Spain
Facility Name
Hospital Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Joan XXIII
City
Tarragona
ZIP/Postal Code
43005
Country
Spain
Facility Name
Hospital La Fe
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Hospital Clinico de Valencia
City
Valencia
ZIP/Postal Code
46011
Country
Spain
Facility Name
Hospital Doctor Peset
City
Valencia
ZIP/Postal Code
46017
Country
Spain
Facility Name
Hospital General de Valencia
City
Valencia
ZIP/Postal Code
46018
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

We'll reach out to this number within 24 hrs