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

NCT ID: NCT01297972

Last Updated: 2014-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-11-30

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.

Conditions

Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Diego Villa Clé

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Diego V Clé, MD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo

Rodrigo T Calado, MD

Role: STUDY_CHAIR

University of Sao Paulo

Locations

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 16778145 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12592355 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26589752 (View on PubMed)

Other Identifiers

CONEP 16119

Identifier Type: -

Identifier Source: org_study_id