Comparison of Cy-Atg vs Flu-Atg for the Conditioning Therapy in Allo-HCT for Adult Aplastic Anemia - Full Text View

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:

MedlinePlus related topics: Anemia Aplastic Anemia Flu

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate

Genetic and Rare Diseases Information Center resources: Aplastic Anemia

U.S. FDA Resources

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

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 (Child, Adult)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

Randomized comparison of cyclophosphamide versus fludarabine in addition to anti-thymocyte globulin for the conditioning therapy in allogeneic hematopoietic cell transplantation for bone marrow failure syndrome This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


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 Cyclophosphamide Fludarabine phosphate Fludarabine Vidarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs	Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on September 26, 2016

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