Clinical trial NCT01956903: Treatment of Refractory Acute Graft-Versus-Host Disease by Sequential Infusion of Allogenic Mesenchymal Stem Cell.
Official title: Phase 1/2 Study of Treatment of Refractory Acute Graft-Versus-Host Disease After First Line Therapy by Sequential Infusion of Expanded In-Vitro Allogenic Mesenchymal Stem Cell
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Graft-Versus-Host Disease
Keywords: mesenchymal stem cell transplantation
Lead sponsor: Grupo Espanol de trasplantes hematopoyeticos y terapia celular
Sponsor class: OTHER
First posted: 2013-10-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of sequential infusion of allogenic mesenchymal stem cells (MSC) expanded "in vitro" in treating patients with acute graft-versus-host disease refractory to first-line therapy.

Detailed description: 1. Ethical considerations:

   * The study will be conducted in accordance with the requirements expressed in the Declaration of Helsinki (Hong Kong revision, September 1989) and following the recommendations of the Good Clinical Practice of the Clinical Trials (document 111/3976/88, July 1990 ) and Spanish legislation (Royal Decree 561/1993, published in April 16th Official State Bulletin "BOE"; May 13th, 1993) laying down the requirements for conducting clinical drug trials.
   * Every subject will receive a written document called "Patient Information Sheet" that contains information about the following aspects of clinical trial: a) Aim of the study, methodology, study treatment and alternative therapies, expected benefits for himself or society, risks of the study and possible adverse events, number of visits and additional tests.

     b) Voluntary nature of their participation and ability to withdraw at any time, without thereby altering the doctor-patient relationship.

     c) People who have access to the data of the volunteer and how they maintain the confidentiality of the data.

     d) How to contact with the investigator if necessary.
   * The investigator will obtain the informed consent of the subject or, failing that, from a legal representative. The subject is preferably expressed written consent or, alternatively, orally to the research team independent witnesses who declare in writing under its responsibility.
   * The person participating in the clinical trial or his representative may revoke the consent at any time.
2. Data Access:

   * In order to ensure the confidentiality of the trial data, only have access to them, the researcher and his team, the test monitor and the Clinical Research Ethics Committee of the corresponding center or purposes under test and relevant health authorities.
   * Protection of data: The content of the data collection forms and the documents generated during the study, will be protected from unauthorized uses by people outside the research and, therefore, will be considered strictly confidential and will not be disclosed to third parties except to those specified in the preceding paragraph.
3. Data Collection:

   * Data colection forms will be dated and signed by the authorized principal investigator.
   * Unknown data will be collected as "NA"(not available).
   * Unusual or extreme results, or that do not match the expected sequence will be checked and corrected by initialing, signing and providing an explanation.
   * Laboratory results that exceed normal limits established by the laboratory of the center, should be checked by the researcher and their significance will be noted next to the data, by initialing and signing.
4. Statistical Analysis:

   * Baseline data will be analyzed using descriptive statistics and demographics (mean, median, standard deviation, minimum, maximum, and number of valid cases) for quantitative variables and absolute and relative frequencies for categorical variables.
   * The primary efficacy objective is to determine the response rate of graft versus host disease (confidence intervals 95%).
   * The primary safety objective is to determine the incidence of adverse events and toxicity related to the administration of the CSM (confidence intervals 95%).
   * Secondary objectives: analyze overall survival and disease-free survival by the Kaplan-Meier method.

Eligibility criteria: Inclusion Criteria:

* Patients with hematologic malignancies who have undergone allogenic stem cell transplantation and who are diagnosed with acute graft-versus-host-disease refractory to first-line treatment.
* Patients must have adequate cardiac function without evidence of uncontrolled hypertension, congestive heart failure or myocardial infarction within 6 months prior to the process.
* Adequate pulmonary function with no evidence of severe obstructive or restrictive pulmonary disease.
* Be able to understand the information and sign the informed consent.

Exclusion Criteria:

* Patients with uncontrolled disease or in progress at the time of treatment.
* Patients with uncontrolled bacterial, viral or fungal infection.
* Patients with inadequate cardiac or pulmonary function.
* Patients who do not have the required donor.
* Women pregnant or at risk of pregnancy by inadequate contraceptive measures.
* Patients who in the opinion of the investigator are not able to participate in the study.

Primary outcomes:
measure: Adverse effects
timeFrame: from infusion to 100 days after stem cell transplant
Secondary outcomes:
measure: efficacy
timeFrame: Acute Graft-Versus-Host Disease period (100 days)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Grupo Espanol de trasplantes hematopoyeticos y terapia celular
Study officials:
affiliation: Hospital Universitario de Salamanca, Salamanca. Spain.
name: Fermín M Sánchez Guijo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clínica Universitaria de Navarra, Spain.
name: Felipe Prosper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra, Spain
name: Eduardo Olavarría, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen del Rocío, Seville, Spain.
name: Rocío Parody, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Puerta del Hierro, Spain
name: Carmen Regidor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i Provincial de Barcelona, Spain
name: Carmen Martínez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de la Santa Creu i Sant Pau, Spain
name: Rodrigo Martino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen del Rocío, Seville, Spain.
name: José Antonio Pérez-Simón, MD
role: PRINCIPAL_INVESTIGATOR
References: