NCT01305694

Brief Summary

The study is a phase I/II trial designed to establish the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells from related donor to patients with relapsed/refractory aplastic anemia.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2011

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

February 28, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 1, 2011

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

March 1, 2011

Status Verified

February 1, 2011

Enrollment Period

1.3 years

First QC Date

February 28, 2011

Last Update Submit

February 28, 2011

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

  • Number of participants with adverse events

    up to 30 days

Secondary Outcomes (4)

  • Hematologic response

    up to 1 year

  • Relapse

    up to 1 year

  • Clonal evolution to PNH, myelodysplasia or acute leukemia

    up to 1 year

  • Survival

    up to 1 year

Study Arms (1)

MSC

EXPERIMENTAL

Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with relapsed/refractory aplastic anemia.

Biological: bone marrow derived mesenchymal stem cells

Interventions

bone marrow derived mesenchymal stem cellsBIOLOGICAL

Intravenous administration of up to 6x10\^5 MSCs per kg,qw,for 4 weeks

Also known as: Mesenchymal Stem Cells, Multipotent Mesenchymal Stem Cells, Multipotent Mesenchymal Stromal Cells
MSC

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must fulfill definition of aplastic anaemia:
  • There must be at least two of the following:
  • haemoglobin \< 100g/L; platelet count \< 50 x 109/L; neutrophil count \< 1.5 x 109/L, and a hypocellular bone marrow;
  • SAA as defined by a hypocellular bone marrow of \<25% cellularity and two of the following:
  • neutrophil count \< 0.5 x 109/L platelets \< 20 x 109/L reticulocytes \< 20 x 109/L nSAA as defined by a hypocellular bone marrow and cytopenia in at least two cell lines and neutrophil count \> 0.5 x 109/L, and red cell and/or platelet transfusion dependence.
  • Patients belong to acquired aplastic anaemia.
  • Patients with a history SAA must have had an incomplete response at least 3 months following treatment with ATG/CsA, or they must have relapsed following an initial response to treatment, and they do not have a HLA-matched donor for bone marrow transplantation. Patients with a history nSAA must have red cell and/or platelet transfusion dependence.
  • Peripheral blood counts at the time of enrollment must include at least one of the following: haemoglobin \< 90 g/L or red blood cell (RBC) transfusion dependence, PMN \< 1 x 109/L, or platelet count \< 50 x 109/L.
  • Patients must have organ function as defined below:
  • total bilirubin within normal institutional limits (NV: 0.0-20.5 umol/L) AST(SGOT)/ALT(SGPT) \< 2.5 × institutional upper limit of normal AST (NV: 0-35 U/L); ALT (NV: 0-40 U/L) Creatinine within normal institutional limits (NV: 53-106 umol/L) or Creatinine clearance \> 1.25 ml/s for patients with creatinine levels above institutional normal.
  • Age minimum 16 years old with no upper age limit.
  • Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

  • Patients may not be receiving any other investigational agents within 4 weeks of study entry.
  • History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells.
  • Current diagnosis of Fanconi's anemia, Dyskeratosis Congenita (DC) or other hereditary forms of AA.
  • Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent.
  • Age \< 16 years old.
  • ECOG performance status \> 2.
  • Malignancy within the last 5 years.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant or breastfeeding women.
  • HIV-positive patients.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Guangzhou General Hospital of Guangzhou Military Command

Guangzhou, Guangdong, 510010, China

RECRUITING

Related Publications (11)

  • Bacigalupo A. Aplastic anemia: pathogenesis and treatment. Hematology Am Soc Hematol Educ Program. 2007:23-8. doi: 10.1182/asheducation-2007.1.23.

    PMID: 18024605BACKGROUND

  • Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002 May 15;99(10):3838-43. doi: 10.1182/blood.v99.10.3838.

    PMID: 11986244BACKGROUND

  • Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008 Jun;38(6):1745-55. doi: 10.1002/eji.200738129.

    PMID: 18493986BACKGROUND

  • English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007 Jun 15;110(2):91-100. doi: 10.1016/j.imlet.2007.04.001. Epub 2007 Apr 26.

    PMID: 17507101BACKGROUND

  • Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007 Aug;149(2):353-63. doi: 10.1111/j.1365-2249.2007.03422.x. Epub 2007 May 22.

    PMID: 17521318BACKGROUND

  • Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005 Feb 15;105(4):1815-22. doi: 10.1182/blood-2004-04-1559. Epub 2004 Oct 19.

    PMID: 15494428BACKGROUND

  • Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007 Jan 1;109(1):228-34. doi: 10.1182/blood-2006-02-002246. Epub 2006 Sep 19.

    PMID: 16985180BACKGROUND

  • Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, Anegon I, Cuturi MC. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood. 2007 Nov 15;110(10):3691-4. doi: 10.1182/blood-2007-02-075481. Epub 2007 Aug 7.

    PMID: 17684157BACKGROUND

  • Gieseke F, Schutt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Muller I. Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood. 2007 Sep 15;110(6):2197-200. doi: 10.1182/blood-2007-04-083162. Epub 2007 May 23.

    PMID: 17522338BACKGROUND

  • Kassis I, Vaknin-Dembinsky A, Karussis D. Bone marrow mesenchymal stem cells: agents of immunomodulation and neuroprotection. Curr Stem Cell Res Ther. 2011 Mar;6(1):63-8. doi: 10.2174/157488811794480762.

    PMID: 20955154BACKGROUND

  • Xiao Y, Jiang ZJ, Pang Y, Li L, Gao Y, Xiao HW, Li YH, Zhang H, Liu Q. Efficacy and safety of mesenchymal stromal cell treatment from related donors for patients with refractory aplastic anemia. Cytotherapy. 2013 Jul;15(7):760-6. doi: 10.1016/j.jcyt.2013.03.007.

    PMID: 23731760DERIVED

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersBone Marrow Diseases

Study Officials

  • Yang Xiao, MD

    Guangzhou General Hospital of Guangzhou Military Command

    STUDY DIRECTOR

Central Study Contacts

Yang Xiao, MD

CONTACT

86-20-36653562jdxiao111@163.com

Li Li, MD

CONTACT

86-20-36652062Lily17155@yahoo.com

Study Design

Study Type
interventional
Phase
phase 1
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

February 28, 2011

First Posted

March 1, 2011

Study Start

February 1, 2011

Primary Completion

June 1, 2012

Study Completion

December 1, 2012

Last Updated

March 1, 2011

Record last verified: 2011-02

Locations

CN(1)