Clinical trial NCT00354120: Thymoglobuline Versus Alemtuzumab in Patients Undergoing Allogeneic Transplant
Official title: Randomized Study for Comparison of Reduced Intensity Conditioning Protocols Containing Either Thymoglobuline or Alemtuzumab in Patients Undergoing Allogeneic Transplant From Voluntary Unrelated Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Myeloblastic Leukemia
Lymphoblastic Leukemia
Myelodysplasia
Chronic Myeloid Leukemia
Myelofibrosis
Lympho-proliferative Diseases
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
First posted: 2006-07-20
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare Reduced Intensity Conditioning protocols containing either Thymoglobuline or Alemtuzumab in patients undergoing allogeneic transplant from voluntary unrelated donors.

Detailed description: The reduction of intensity of conditioning is currently indicated for patients who cannot undergo standard myelo-ablation due to their age, comorbidities or type of pathology. Furthermore, the rationale to use RIC regimens is based on the observation that the infusion of alloreactive donor lymphocytes may yield to a graft versus tumour effect. However, in this kind of regimens the morbidity and TRM due to GvHD are still a concern and in vivo T-depletion is a necessary treatment. Both monoclonal (Alemtuzumab) and polyclonal T-depletion protocols carry risks and benefits. Benefits being a better prophylaxis for GvHD, and risks being an higher incidence of post-transplantation infections and relapse. At the moment, it is not clear which type of regimen, monoclonal or polyclonal, is better for the treatment.

Eligibility criteria: Inclusion Criteria:

* Group 1: 55-65 yo patients suffering from Acute Myeloblastic and Lymphoblastic Leukemia, Myelo-displasia, Chronic Myeloid Leukemia and Idiopathic Myelofibrosis (according to IBMDR operative manual)
* Group 2: patients \<= 65 yo suffering from lympho-proliferative diseases according the REAL classification:
* High-doses chemotherapy relapsed CLL (B and T)
* Follicular lymphoma relapsed after 2 standard chemotherapy regimens or after high-doses chemotherapy
* Mantellar lymphoma relapsed after 1 standard chemotherapy regimen or after high-doses chemotherapy
* Lympho-plasmacytoid and B marginal zone lymphoma in relapse after 2 standard chemotherapy regimens or after high-doses chemotherapy
* Advanced (stage ≥ III A) or relapsed T lymphomas
* Large B-cells lymphomas in 2nd or further complete remission after relapse from high dose chemotherapy and autotransplant or after 2 standard chemotherapy regimens
* Fungal mycosis in advanced stage (≥ III A) or in chemosensitive relapse after 2 lines of chemotherapy and Sezary syndrome in chemosensitive relapse after 1 line of chemotherapy
* Hodgkin disease relapse after autotransplant with chemosensitive disease or in relapse after 1 year from chemotherapy and not eligible for autotransplant since an insufficient mobilization of autologous hemopoietic stem cells.

Exclusion Criteria:

* Performance status \< 70% (Karnofsky)
* Left ventricular cardiac ejection fraction \< 40% or receiving treatment for heart failure
* DLCO pulmonary \< 40% or receiving continuous oxygen therapy
* Neuropathy (previous or at present)
* Pregnancy
* Patients with arterial hypertension not controlled with multi-pharmacological treatments
* HIV positive
* B-CLL with clear evidence of transformation into Richter syndrome
* Mycosis fungoides with clear evidence of transformation into blasts
* Hodgkin's disease refractory to chemotherapy
* Absence of informed consent
* Psychiatric disease or other condition compromising the signing of the informed consent form or compliance with the treatment

Primary outcomes:
measure: Overall Survival
timeFrame: 3 years
measure: Event Free Survival and Disease Free Survival
timeFrame: 3 years
measure: Safety:
timeFrame: 3 years
measure: Major infective complications (CMV and EBV related PTLD)
timeFrame: 3 years
measure: Acute and chronic GvHD
timeFrame: 3 years
Secondary outcomes:
measure: Haematological and immunologic reconstitution
timeFrame: 3 years
measure: Incidence of CMV and EBV reactivation
timeFrame: 3 years
measure: Other infective complications
timeFrame: 3 years
measure: Other toxicities
timeFrame: 3 years
measure: Need for DLI
timeFrame: 3 years
Other outcomes:
Locations:
city: San Giovanni Rotondo
country: Italy
facility: Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza
state: Foggia
city: Alessandria
country: Italy
facility: Divisione Ematologia - Ospedale "SS. Antonio, Biagio e Cesare Arrigo"
city: Ancona
country: Italy
facility: Clinica di Ematologia - Ospedali Riuniti di Ancona
city: Bergamo
country: Italy
facility: Divisione di Ematologia - Ospedali Riuniti Bergamo
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: Cattedra di Ematologia - Azienda Ospedaliera di Careggi
city: Genova
country: Italy
facility: Trapianti Midollo Osseo - Div. di Ematologia 2 - Ospedale S. Martino
city: Milano
country: Italy
facility: Divisione di Ematologia - Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: U.O. Ematologia I - Centro Trapianti di Midollo - Ospedale Maggiore - Policlinico Mangiagalli e Regina Elena
city: Modena
country: Italy
facility: Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -
city: Monza
country: Italy
facility: Cattedra di Medicina Interna ed Ematologia - Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano
city: Palermo
country: Italy
facility: Divisione Ematologia con trapianto - Ospedale "V. Cervello"
city: Pavia
country: Italy
facility: Dipartimento di Ematologia - IRCCS Policlinico S. Matteo - Università di Pavia
city: Pescara
country: Italy
facility: Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara
city: Pisa
country: Italy
facility: Ematologia - Ospedale S. Chiara
city: Reggio Calabria
country: Italy
facility: Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli
city: Roma
country: Italy
facility: Cattedra di Ematologia - Università La Sapienza
city: Roma
country: Italy
facility: Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli
city: Roma
country: Italy
facility: U.O. di Ematologia e Trapianti di Midollo Osseo - Azienda Osp. S. Camillo-Forlanini / Padiglione Morgagni
city: Rozzano (MI)
country: Italy
facility: Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Ematologia 2 - ASO San Giovanni Battista
city: Udine
country: Italy
facility: Clinica Ematologica - Policlinico Universitario
Study officials:
affiliation: Divisione di Ematologia - Ospedali Riuniti di Bergamo
name: Alessandro Rambaldi, MD
role: STUDY_CHAIR
References: