Clinical trial NCT00781781: Alemtuzumab Use (MabCampath®) in Hematopoietic Transplant of Unrelated Donor With Reduced Intensity Conditioning
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Keywords: Myeloid and Lymphoid malignances
Lead sponsor: CABYC
Sponsor class: INDUSTRY
Collaborators: name: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
First posted: 2008-10-29
Enrollment: 34
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Analyze the results of incidence and severity of acute and chronic GVHD
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial.
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Comunidad Valenciana
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Vall de Hebron
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
Study officials:
affiliation: ICO Bellvitge. Hospital Duran i Reynals
name: Rafael Duarte, MD, Ph.D
role: STUDY_DIRECTOR
References: