NCT01145976

Brief Summary

The purpose of this study is to reduce the regimen related toxicities and transplantation related mortality after allogeneic stem cell transplantation in adult acquired aplastic anemia (AA), the trials of reduced dose of Cy along with fludarabine and ATG were performed.11-21 The investigators preliminary data of randomized comparison of cyclophosphamide plus fludarabine versus cyclophosphamide alone in addition to anti-thymocyte globulin for the conditioning therapy in allogeneic hematopoietic cell transplantation for bone marrow failure syndrome supports reduced dose of Cy along with fludarabine and ATG. Conditioning regimen without Cy may reduce RRT because Cy-containing conditioning remains several RRT such as hemorrhagic cystitis, SOS and graft versus host disease (GvHD). Recently there were small trials of fludarabine and ATG (Flu-ATG) for the conditioning regimen of alloHSCT.22-24 These data raised the feasibility of fludarabine and ATG without Cy for patients with AA. This new conditioning regimen of Flu-ATG will be compared to standard regimen of Cy- ATG in a randomized controlled trial.

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
98

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Mar 2010

Longer than P75 for phase_3

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

March 1, 2010

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

May 19, 2010

Completed
29 days until next milestone

First Posted

Study publicly available on registry

June 17, 2010

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

September 7, 2012

Status Verified

September 1, 2012

Enrollment Period

4.9 years

First QC Date

May 19, 2010

Last Update Submit

September 6, 2012

Conditions

Aplastic Anemia

Keywords

aplastic anemia, fludarabine, cyclophosphamide, thymoglobulin

Outcome Measures

Primary Outcomes (1)

  • regimen-related toxicities(RRT)

    * The RRTs will be evaluated in terms of mucositis, hemorrhagic cystitis, SOS, acute graft versus host disease (GvHD), infection rate, graft failure, time to engraftment. * Overall feasibility will be evaluated by RRTs, time to engraftment, chronic GvHD, treatment-related mortality (TRM), relapse rate, infertility, chimerism status, changes of hemostatic variables, event-free survival and overall survival.

    7 years

Secondary Outcomes (1)

  • Overall feasibility

    7 years

Study Arms (2)

CY-ATG(Arm1)

ACTIVE COMPARATOR

Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2

Drug: Cy-ATG

Flu-ATG(Arm2)

EXPERIMENTAL

Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 6 consecutive days (days -7 to -2) Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2

Drug: Flu-ATG

Interventions

Cy-ATGDRUG

Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2

Also known as: Cyclophosphamide, Thymoglobulin
CY-ATG(Arm1)
Flu-ATGDRUG

Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 6 consecutive days (days -7 to -2) Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2

Also known as: Fludarabine, Thymoglobulin
Flu-ATG(Arm2)

Eligibility Criteria

Age15 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Severe aplastic anemia
  • Severe aplastic anemia (SAA) is defined as a hypocellular bone marrow (cellularity\<25%) and two or more of the following: granulocyte count \<500/ml, platelet count \<20,000/ml, and corrected reticulocyte count \<1.0%
  • Very severe aplastic anemia (VSAA) is defined as the criteria for SAA plus a granulocyte count \<200/ml
  • Patients should be 15 years of age or older, but younger than 65 years.
  • The performance status of the patients should be 70 or over by Karnofsky performance scale (see Appendix I).
  • Patients must have adequate hepatic function (bilirubin less than 2 mg/dl, AST and ALT less than three times the upper normal limit)
  • Patients must have adequate renal function (creatinine less than 2.0 mg/dl).
  • Patients must have adequate cardiac function (ejection fraction \> 45% on echocardiogram).

You may not qualify if:

  • Patients should not have major illness or organ failure.
  • Patients must not have a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlikely, and making informed consent impossible.
  • Patients must not be in pregnancy.
  • Hypoplastic myelodysplastic syndrome
  • Paroxysmal nocturnal hemoglobinuria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 138-736, South Korea

RECRUITING

Related Publications (1)

  • Kim H, Lee JH, Joo YD, Bae SH, Hyun MS, Lee JH, Kim DY, Lee WS, Ryoo HM, Kim MK, Park JH, Lee KH; Cooperative Study Group A for Hematology (COSAH). A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome. Ann Hematol. 2012 Sep;91(9):1459-69. doi: 10.1007/s00277-012-1462-x. Epub 2012 Apr 18.

    PMID: 22526363DERIVED

Related Links

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Cyclophosphamidethymoglobulinfludarabine

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Hawk Kim, professor

    Ulsan University Hospital, University of Ulsan College of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Hawk Kim, M.D., Ph.D.

CONTACT

82-52-250-8892kimhawkmd@gmail.com

Je-Hwan Lee, M.D., Ph.D.

CONTACT

jhlee3@amc.seoul.kr

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research nurse

Study Record Dates

First Submitted

May 19, 2010

First Posted

June 17, 2010

Study Start

March 1, 2010

Primary Completion

February 1, 2015

Study Completion

February 1, 2016

Last Updated

September 7, 2012

Record last verified: 2012-09

Locations

KR(1)