Thymoglobuline Versus Alemtuzumab in Patients Undergoing Allogeneic Transplant

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Study for Comparison of Reduced Intensity Conditioning Protocols Containing Either Thymoglobuline or Alemtuzumab in Patients Undergoing Allogeneic Transplant From Voluntary Unrelated Donors

Conditions
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Myelodysplasia, Acute Myeloblastic Leukemia, Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Myelofibrosis, Lympho-proliferative Diseases

Intervention / Treatment
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* Drug: Alentuzumab
* Drug: Globulina antilinfocitaria


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Alentuzumab | Drug: Alentuzumab<br>* Alentuzumab<br>|
| Active Comparator: 2<br>Globulina antilinfocitaria | Drug: Globulina antilinfocitaria<br>* Globulina antilinfocitaria<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 3 years | 
| Event Free Survival and Disease Free Survival |  | 3 years | 
| Safety: |  | 3 years | 
| Major infective complications (CMV and EBV related PTLD) |  | 3 years | 
| Acute and chronic GvHD |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematological and immunologic reconstitution |  | 3 years | 
| Incidence of CMV and EBV reactivation |  | 3 years | 
| Other infective complications |  | 3 years | 
| Other toxicities |  | 3 years | 
| Need for DLI |  | 3 years |