Comparison of Cy-Atg vs Flu-Atg for the Conditioning Therapy in Allo-HCT for Adult Aplastic Anemia (CyATG-FluATG)

This study is currently recruiting participants.
Verified September 2012 by Cooperative Study Group A for Hematology
Sponsor:
Information provided by (Responsible Party):
Yae Eun Jang, Cooperative Study Group A for Hematology
ClinicalTrials.gov Identifier:
NCT01145976
First received: May 19, 2010
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Aplastic Anemia
Drug: Cy-ATG
Drug: Flu-ATG
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Comparison of Cyclophosphamide Versus Fludarabine in Addition to Anti-thymocyte Globulin for the Conditioning Therapy in Allogeneic Hematopoietic Cell Transplantation for Adult Acquired Aplastic Anemia

Resource links provided by NLM:


Further study details as provided by Cooperative Study Group A for Hematology:

Primary Outcome Measures:
  • regimen-related toxicities(RRT) [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    • 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.


Secondary Outcome Measures:
  • Overall feasibility [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    Day 100 mortality rate, overall survival


Estimated Enrollment: 98
Study Start Date: March 2010
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CY-ATG(Arm1)

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

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

Other Names:
  • Cyclophosphamide
  • Thymoglobulin
Experimental: Flu-ATG(Arm2)
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
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
Other Names:
  • Fludarabine
  • Thymoglobulin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Exclusion criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01145976

Contacts
Contact: Hawk Kim, M.D., Ph.D. 82-52-250-8892 kimhawkmd@gmail.com
Contact: Je-Hwan Lee, M.D., Ph.D. jhlee3@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Songpa-gu, Korea, Republic of, 138-736
Contact: Yae Eun Jang, Nurse    82-2-3010-6378    redpin75@paran.com   
Sponsors and Collaborators
Cooperative Study Group A for Hematology
Investigators
Principal Investigator: Hawk Kim, professor Ulsan University Hospital, University of Ulsan College of Medicine
  More Information

Additional Information:
No publications provided by Cooperative Study Group A for Hematology

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yae Eun Jang, Research nurse, Cooperative Study Group A for Hematology
ClinicalTrials.gov Identifier: NCT01145976     History of Changes
Other Study ID Numbers: C-021
Study First Received: May 19, 2010
Last Updated: September 6, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Cooperative Study Group A for Hematology:
aplastic anemia, fludarabine, cyclophosphamide, thymoglobulin

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 16, 2014