R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

NCT00504491 | Withdrawn Phase 2 DMC

• 2 other identifiers: GELLC-22007-003097-26
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 32

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.

Conditions

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

Keywords

Rituximab-CHOP; Alemtuzumab; Chronic lymphocytic leukaemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

Rituximab-CHOP-Alemtuzumab DRUG

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

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Enlarged lymph nodes or giant node clusters (\>10 cm in diameter) or progressive growth lymph nodes.
• Giant splenomegaly (\> 6 cm under ribs border) or progressive splenomegaly.
• Progressive lymphocytosis (\>50% increase in a period of 2 months) or lymphocyte duplication time (expected) \< 6 months
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CABYC: lead
• Francesc Bosch, MD: collaborator
• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: collaborator
• Fundacion Clinic per a la Recerca Biomédica: collaborator
• Bayer: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (32)

Hospital de Son Dureta

Palma de Mallorca, Balearic Islands, 07014, Spain

Location

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Hospital Valle de Hebron

Barcelona, Barcelona, 08035, Spain

Location

ICO Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Althaia

Manresa, Barcelona, 08243, Spain

Location

Corporacion Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Hospital de Basurto

Bilbao, Bilbao, 48013, Spain

Location

Hospital Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Clinic i Provincial.

Barcelona, Catalonia, 08036, Spain

Location

ICO Gerona

Girona, Girona, 17007, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Gran Canaria, 38320, Spain

Location

Hospital Virgen de las Nieves

Granada, Granada, 18014, Spain

Location

Hospital Arnau de Vilanova

Lleida, Lleida, 25198, Spain

Location

Hospital La Princesa

Madrid, Madrid, 28006, Spain

Location

Hospital Gregorio Marañon

Madrid, Madrid, 28007, Spain

Location

M.D.Anderson Internacional

Madrid, Madrid, 28033, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital 12 de octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Morales Meseguer

Murcia, Murcia, 30008, Spain

Location

Hospital Clinico de Salamanca

Salamanca, Salamanca, 37007, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, Santiago de Compostela, 36680, Spain

Location

Hospital Virgen del Rocio

Seville, Sevilla, 41013, Spain

Location

Hospital Joan XXIII

Tarragona, Tarragona, 43005, Spain

Location

Hospital Francisco de Borja

Gandia, Valencia, 46700, Spain

Location

Hospital La Fe

Valencia, Valencia, 46009, Spain

Location

Hospital Clinico de Valencia

Valencia, Valencia, 46011, Spain

Location

Hospital Doctor Peset

Valencia, Valencia, 46017, Spain

Location

Hospital General de Valencia

Valencia, Valencia, 46018, Spain

Location

Hospital Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Leukemia, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francesc Bosch, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2007
• First Posted: July 20, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 30, 2011

Record last verified: 2011-12

Locations

ES (32)