Clinical trial NCT01297972: Mesenchymal Stem Cells in the Treatment of Relapsed/Refractory Severe Acquired Aplastic Anemia
Official title: Bone Marrow Mesenchymal Stem Cells in the Treatment of Refractory Severe Acquired Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Aplastic Anemia
Keywords: Aplastic Anemia
Mesenchymal Stem Cells
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2011-02-17
Enrollment: 9
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: Mesenchymal stem cells have been tested in many autoimmune disorders with encouraging results and may be an alternative to the treatment of immune-mediated severe acquired aplastic anemia.

Detailed description: Acquired aplastic anemia is a bone marrow failure syndrome characterized by and empty bone marrow and low blood counts. Most of the cases are immune-mediated. Allogeneic bone marrow transplant is the preferable treatment modality for patients younger than 40 years with a matched sibling donor. Patients not eligible for transplant are treated with intensive immunosuppressive therapy often based on anti-thymocyte globulin and cyclosporine.

However, up to one third of patients treated with immunosuppression are refractory and one third of those who response eventually relapse. Refractory and relapsed cases may be the result of insufficient immunosuppression and these cases may benefit from additional immunosuppression. Mesenchymal stem cells infusion may be a potential treatment option, considering its properties to modulate the immune system.

Refractory or relapsed patients with aplastic anemia will be treated with conventional immunosuppressive regimen (anti-thymocyte globulin plus cyclosporine) combined with intravenous infusion of allogeneic unrelated bone marrow mesenchymal stem cells.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Acquired Aplastic Anemia
* Relapse/refractory to at least 1 immunosuppressive first line treatment
* Not eligible to allogeneic bone marrow transplantation

Exclusion Criteria:

* Previous or current malignancy
* Active or latent infectious disease
* Positive serologic tests for HIV, HCV, HBV, HTLV-1 and 2, Syphilis or Chagas disease
* Previous drug reaction for antithymocyte globulin, cyclosporin or corticosteroids
* Severe organic impairment (renal, hepatic, cardiac, pulmonary)
* Uncontrolled hypertension or diabetes
* Pregnancy
* Previous history of allergic reaction to penicillin or streptomycin
* Severe psychiatric disorder

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of intravenous allogeneic unrelated mesenchymal stem cells infusion in patients with severe acquired aplastic anemia.
timeFrame: After the mesenchymal stem cells infusion up to 6 mounth after
Secondary outcomes:
measure: Level of cytopenias
timeFrame: weekly until 6 months
measure: Transfusional requirements
timeFrame: weekly until 6 months
measure: Incidence of infections and febrile neutropenia
timeFrame: weekly until 6 months
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Diego V Clé, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sao Paulo
name: Rodrigo T Calado, MD
role: STUDY_CHAIR
References:
citation: Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19. doi: 10.1182/blood-2006-03-010777. Epub 2006 Jun 15.
citation: Fouillard L, Bensidhoum M, Bories D, Bonte H, Lopez M, Moseley AM, Smith A, Lesage S, Beaujean F, Thierry D, Gourmelon P, Najman A, Gorin NC. Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma. Leukemia. 2003 Feb;17(2):474-6. doi: 10.1038/sj.leu.2402786. No abstract available.
citation: Cle DV, Santana-Lemos B, Tellechea MF, Prata KL, Orellana MD, Covas DT, Calado RT. Intravenous infusion of allogeneic mesenchymal stromal cells in refractory or relapsed aplastic anemia. Cytotherapy. 2015 Dec;17(12):1696-705. doi: 10.1016/j.jcyt.2015.09.006.