Alemtuzumab Use (MabCampath®) in Hematopoietic Transplant of Unrelated Donor With Reduced Intensity Conditioning

Multicenter, Openlabel, Phase II Intergroups (GELTAMO/GETH) Trial, on the Use of Alemtuzumab for Unrelated Donor Reduced Intensity Conditioning Allogenic Transplant in Hematological Malignancies Patients

The purpose of this study is to analyze the results of incidence and severity of acute and chronic GVHD, (see addendum II) and of disease free survival with Alemtuzumab use (MabCampath®) in haematopoietic transplant of unrelated donor with reduced intensity conditioning.

Study Overview

• Status: Terminated
• Conditions: Graft Versus Host Disease
• Intervention / Treatment: Drug: Alemtuzumab

Detailed Description

Each patient will be assigned to one of the two dosing schedules and total dose of drug envisaged in the study. The assignation to conventional or reduced Alemtuzumab (MabCampath) dose will be done depending on the age and risk of suffering GVHD, in function of variables coming from general experience.

High risk of GVHD criteria:

Gender incompatibility: male patient of female donor. HLA incompatibility: non identical high resolution typing in HLA A, B, C, DRB1, DQB1 (identity less than 10/10 alleles by high resolution) Age of patient more or equal than 55 years

Conventional doses in high risk (at least one criterion of GVHD high risk):

100 mg de Alemtuzumab IV total dose in 5, 20 mg fractions, days -8, -7, -6, -5 and -4.

Reduced dose in low risk cases (no criteria of GVHD high risk):

50 mg de Alemtuzumab IV total dose en 5 fractions of 10 mg, days -5, -4, -3, -2 and -1.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain
    • Vall de Hebron
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañón
  • Madrid, Spain, 28006
    • Hospital La Princesa
  • Murcia, Spain, 30008
    • Hospital Morales Meseguer
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • ICO Bellvitge
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Hospital Clinic i Provincial.
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Hospital Clinico de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients with haematological or lymphoid malignancies with allogenic transplantation indication:

  • High risk follicular NHL, mantle HHC and other low grade NHC (e.g lymphoplasmacytic, extranodal or from marginal zone).

    1. Disease that does not obtain a CR with Fludarabine or antiCD-20 including chemotherapy.
    2. Relapse after autologous transplant.
    3. Non candidates to autologous transplant in 2nd CR (e.g. mobilization failure, or persistent marrow infiltrate).
  • Poor prognosis chronic lymphoblastic leukaemia (CLL): Del 11q, Del 17p, complex cariotype; B symptoms, progressive low cell count by marrow infiltration, lymphocytosis or enlarged lymph nodes, or progressive spleen growth.
  • High grade lymphoma transformed from a low grade non Hodgkin's lymphoma or from a chronic lymphocitic leukaemia
  • High risk T peripheral lymphoma, with IPI > or = 2, non susceptible of autologous transplant, or relapsed after autologous transplant
  • Primarily refractory high risk Hodgkin's disease, relapse in patients not susceptible of autologous transplant or relapse after autologous transplant.
  • High risk acute mieloblastic leukaemia (AML) in 1st CR, or AMC > or = 2 CR, including AML after MDS and secondary AML.
  • High risk acute lymphoblastic leukaemia (ALL) because of poor response to induction chemotherapy (>10% blasts day +14 or no RC day +28-35), or by cytogenetic criteria: Ph+ or 11q23.
  • High risk myelodisplastic syndromes (SMD) type RAEB-1 or AREB-2 with IPSS >Int-1.
• For the inclusion in transplant patients with ALL or AML must be in CR, patients with MDS must have <10% blasts en la BM, and patients with lymphoid malignancies must show previous chemosensitivity, with PR or CR.
• Patients 40 to 65 years old. Patients outside this age range could be included according to participating centres criteria.
• Patients in the study population lacking a compatible related donor, and with a possible compatible unrelated donor (>=9/10 by 10 alleles high resolution typing: HLA-A, B, C, DRB1, DQB1) to assign the patients to a risk in subgroup.
• Signed informed consent.
• Not fulfilling any of the following exclusion criteria.

Exclusion Criteria:

• Liver (≥ x3 UNL), kidney (GF <40ml/min), cardiac (LVEF <40%) or respiratory (DLCO & FVC <40% of expected) function tests impairment.
• HIV injection.
• Absence of signed informed consent.
• Progressive disease previous to transplant or not fulfilling the above mentioned response criteria.
• Other co-morbidities that contraindicate CT.
• Pregnant and/or breast-feeding women or with pregnancy risk by inadequate contraception.
• Life expectancy <6 months.
• Mental or psychiatric deficiency impeding adequate understanding and consent to therapy
• Hypersensitivity as shown by anaphylactic reaction to any of the DRUGS used in the trial.
• Active infectious process.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; High risk patients (at least one GVHD high risk criterion): Total dose 100 mg in 5 doses of 20 mg, days -8 to -4 (inclusive).	Drug: Alemtuzumab; High risk: Total dose 100 mg in 5 doses of 20 mg, days -8 to -4 (inclusive) Low risk: Total dose 50 mg inn 5 dosing OF 10 mg, days -5 to -1 (inclusive).; Other Names: MabCampath
Experimental: 2; Low Risk patients (no GVHD high risk criterion): Total dose 50 mg inn 5 dosing OF 10 mg, days -5 to -1 (inclusive).	Drug: Alemtuzumab; High risk: Total dose 100 mg in 5 doses of 20 mg, days -8 to -4 (inclusive) Low risk: Total dose 50 mg inn 5 dosing OF 10 mg, days -5 to -1 (inclusive).; Other Names: MabCampath

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Analyze the results of incidence and severity of acute and chronic GVHD	3 years

Collaborators and Investigators

• Sponsor: CABYC
• Collaborators: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Investigators: Study Director: Rafael Duarte, MD, Ph.D, ICO Bellvitge. Hospital Duran i Reynals

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 28, 2008
• First Submitted That Met QC Criteria: October 28, 2008
• First Posted (Estimate): October 29, 2008

Study Record Updates

• Last Update Posted (Estimate): February 4, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Myeloid and Lymphoid malignances
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Antineoplastic Agents; Antineoplastic Agents, Immunological; Alemtuzumab
• Other Study ID Numbers: ALOTIRNE-EC06007; 2007-006440-22 (EudraCT Number)