Mesenchymal Stem Cells in the Treatment of Relapsed/Refractory Severe Acquired Aplastic Anemia

Aplastic Anemia Clinical Trial

Official title:

Bone Marrow Mesenchymal Stem Cells in the Treatment of Refractory Severe Acquired Aplastic Anemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297972
• Other study ID #: CONEP 16119
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 16, 2011
• Last updated: February 2, 2014
• Start date: February 2011
• Est. completion date: November 2013

Study information

• Verified date: February 2014
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Biological:
• Intravenous bone marrow mesenchymal stem cells infusion
After standard immunosuppressive therapy with rabbit antithymocyte globulin 3,5 mg/Kg/day during 5 days, allogeneic unrelated bone marrow derived mesenchymal stem cells will be infused intravenously. Oral cyclosporine 5 mg/Kg/day (with dose correction weekly to keep serum cyclosporine level between 150-250 mg/dl) up to 6 months will be added.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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. — View 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. Epub 2006 Jun 15. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Adverse events like allergic reactions,infectious diseases,organ dysfunction or other related to mesenchymal stem cells infusion will be assessed.	After the mesenchymal stem cells infusion up to 6 mounth after	Yes
Secondary	Level of cytopenias		weekly until 6 months	No
Secondary	Transfusional requirements	Units of blood or platelets transfused after the mesenchymal stem cells infusion will be measured and compared to previously.	weekly until 6 months	No
Secondary	Incidence of infections and febrile neutropenia		weekly until 6 months	No