NCT01759732

Brief Summary

Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion of CD3 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation. Purpose: Phase II trials to evaluate the efficacy of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe 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
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Sep 2012

Typical duration for phase_2

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

September 1, 2012

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

December 30, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 3, 2013

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

January 3, 2013

Status Verified

December 1, 2012

Enrollment Period

2.2 years

First QC Date

December 30, 2012

Last Update Submit

December 30, 2012

Conditions

Keywords

Aplastic anemiaT cell doseCD3 depletionHaploidentical hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

  • To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia

    2 years posttransplant

Secondary Outcomes (4)

  • To assess engraftment and graft failure

    28 days posttransplant

  • To estimate the risk of acute GVHD

    100 days posttransplant

  • To assess treatment related mortality

    100 days posttransplant

  • To estimate overall survival and failure free survival

    1 year posttransplant

Study Arms (1)

HAPLO

EXPERIMENTAL
Drug: FludarabineDrug: CyclophosphamideBiological: anti-thymocyte globulinBiological: filgrastimRadiation: Total body irradiationProcedure: CD3-depleted hematopoietic cell transplantation

Interventions

40mg/M2 once daily IV on days -7 to -4

HAPLO

60 mg/kg IV on day-3 and -2

HAPLO
filgrastimBIOLOGICAL
Also known as: Beginning on day 4 and continuing until blood counts recover
HAPLO

200 cGy per day on D-5 \& -4

HAPLO

Immunogenetic depletion on CliniMACS

HAPLO

Eligibility Criteria

AgeUp to 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:
  • Granulocyte count \< 500/mm3,
  • Corrected reticulocyte count \< 1%,
  • Platelet count \< 20,000/mm3
  • No HLA-identical family member or closely matched (8 of 8 HLA-locus match) unrelated marrow donor available
  • HLA-haploidentical related donor available

You may not qualify if:

  • Paroxysmal nocturnal hemoglobinuria or Fanconi anemia
  • Clonal cytogenetic abnormalities or myelodysplastic syndromes
  • Active fungal infections
  • HIV positive
  • Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
  • Pregnant or nursing

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

RECRUITING

Related Publications (5)

  • Burroughs LM, Woolfrey AE, Storer BE, Deeg HJ, Flowers ME, Martin PJ, Carpenter PA, Doney K, Appelbaum FR, Sanders JE, Storb R. Success of allogeneic marrow transplantation for children with severe aplastic anaemia. Br J Haematol. 2012 Jul;158(1):120-8. doi: 10.1111/j.1365-2141.2012.09130.x. Epub 2012 Apr 26.

    PMID: 22533862BACKGROUND
  • Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty JM, Adams RH, Ewell M, Leifer ES, Gersten ID, Carter SL, Horowitz MM, Nakamura R, Pulsipher MA, Difronzo NL, Confer DL, Eapen M, Anderlini P. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biol Blood Marrow Transplant. 2012 Jul;18(7):1007-11. doi: 10.1016/j.bbmt.2012.04.014. Epub 2012 Apr 27.

    PMID: 22546497BACKGROUND
  • Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant. 2012 Dec;47(12):1507-12. doi: 10.1038/bmt.2012.79. Epub 2012 May 28.

    PMID: 22635243BACKGROUND
  • Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. No abstract available.

  • Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients. Bone Marrow Transplant. 2015 Feb;50(2):225-31. doi: 10.1038/bmt.2014.232. Epub 2014 Oct 13.

Related Links

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

fludarabineCyclophosphamideAntilymphocyte SerumFilgrastimWhole-Body Irradiation

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesGranulocyte Colony-Stimulating FactorColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological FactorsRadiotherapyTherapeuticsInvestigative Techniques

Study Officials

  • Ho Joon Im, MD, PhD

    Asan Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ho Joon Im, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

December 30, 2012

First Posted

January 3, 2013

Study Start

September 1, 2012

Primary Completion

December 1, 2014

Study Completion

December 1, 2015

Last Updated

January 3, 2013

Record last verified: 2012-12

Locations