R-CHOP and Alemtuzumab in Patients With Chronic Lymphocytic Leukemia

• Sponsor: CABYC (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT00504491
• Collaborator: Francesc Bosch, MD (Other), Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea (Other), Fundacion Clinic per a la Recerca Biomédica (Other), Bayer (Industry), Genzyme, a Sanofi Company (Industry)
• Enrollment: 0
• Locations: 32
• Arm: 1
• Duration (Months): 59
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

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.

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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jul 1, 2007
• Anticipated Primary Completion Date: Jan 1, 2012
• Anticipated Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. Patients previously treated in first line with purine analogous and showing:

• Treatment failure (stable disease or progression)

• Relapse within three years of therapy.

1. 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

Locations

	Site	City	State	Country	Postal Code
1	ICO Badalona	Badalona	Barcelona	Spain	08916
2	ICO Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
3	Althaia	Manresa	Barcelona	Spain	08243
4	Corporacion Sanitaria Parc Tauli	Sabadell	Barcelona	Spain	08208
5	Hospital Clinic i Provincial.	Barcelona	Cataluña	Spain	08036
6	Hospital Universitario de Canarias	La Laguna	Gran Canaria	Spain	38320
7	Hospital de Son Dureta	Palma de Mallorca	Islas Baleares	Spain	07014
8	Hospital Francisco de Borja	Gandia	Valencia	Spain	46700
9	Hospital del Mar	Barcelona		Spain	08003
10	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08025
11	Hospital Valle de Hebron	Barcelona		Spain	08035
12	Hospital de Basurto	Bilbao		Spain	48013
13	ICO Gerona	Girona		Spain	17007
14	Hospital Virgen de las Nieves	Granada		Spain	18014
15	Hospital Arnau de Vilanova	Lleida		Spain	25198
16	Hospital La Princesa	Madrid		Spain	28006
17	Hospital Gregorio Marañon	Madrid		Spain	28007
18	M.D.Anderson Internacional	Madrid		Spain	28033
19	Hospital Ramón y Cajal	Madrid		Spain	28034
20	Hospital Clínico San Carlos	Madrid		Spain	28040
21	Hospital 12 de octubre	Madrid		Spain	28041
22	Hospital Morales Meseguer	Murcia		Spain	30008
23	Hospital Clinico de Salamanca	Salamanca		Spain	37007
24	Hospital Marques de Valdecilla	Santander		Spain	39008
25	Hospital Clinico Universitario de Santiago	Santiago de Compostela		Spain	36680
26	Hospital Virgen del Rocio	Sevilla		Spain	41013
27	Hospital Joan XXIII	Tarragona		Spain	43005
28	Hospital La Fe	Valencia		Spain	46009
29	Hospital Clinico de Valencia	Valencia		Spain	46011
30	Hospital Doctor Peset	Valencia		Spain	46017
31	Hospital General de Valencia	Valencia		Spain	46018
32	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 of Barcelona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CABYC
• ClinicalTrials.gov Identifier: NCT00504491
• Other Study ID Numbers: GELLC-2; 2007-003097-26
• First Posted: Jul 20, 2007
• Last Update Posted: Dec 30, 2011
• Last Verified: Dec 1, 2011

• Keywords provided by CABYC: Rituximab-CHOP; Alemtuzumab; Chronic lymphocytic leukaemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Alemtuzumab

Study Results

No Results Posted as of Dec 30, 2011