R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukaemia Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00504491
• Other study ID #: GELLC-2
• Secondary ID: 2007-003097-26
• Status: Withdrawn
• Phase: Phase 2
• First received: July 19, 2007
• Last updated: December 28, 2011
• Start date: July 2007
• Est. completion date: June 2012

Study information

• Verified date: December 2011
• Source: CABYC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukaemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Patients Relapsed With Purines Therapy
• Patients Resistant to a Purine Analogous

Intervention

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

Locations

Country	Name	City	State
Spain	ICO Badalona	Badalona	Barcelona
Spain	Hospital Clinic i Provincial.	Barcelona	Cataluña
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Valle de Hebron	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital Francisco de Borja	Gandia	Valencia
Spain	ICO Gerona	Girona
Spain	Hospital Virgen de las Nieves	Granada
Spain	ICO Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Canarias	La Laguna	Gran Canaria
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Hospital 12 de octubre	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	M.D.Anderson Internacional	Madrid
Spain	Althaia	Manresa	Barcelona
Spain	Hospital Morales Meseguer	Murcia
Spain	Hospital de Son Dureta	Palma de Mallorca	Islas Baleares
Spain	Corporacion Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Clinico de Salamanca	Salamanca
Spain	Hospital Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Joan XXIII	Tarragona
Spain	Hospital Clinico de Valencia	Valencia
Spain	Hospital Doctor Peset	Valencia
Spain	Hospital General de Valencia	Valencia
Spain	Hospital La Fe	Valencia
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (6)

Lead Sponsor	Collaborator
CABYC	Bayer, Francesc Bosch, MD, Fundacion Clinic per a la Recerca Biomédica, Genzyme, a Sanofi Company, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		57 months