Cyclophosphamide, Fludarabine and Antithymocyte Globulin Conditioning in Myelodysplastic Syndrome (MDS)

Myelodysplastic Syndrome Clinical Trial

— CyFluATG  

Official title:

Conditioning With Cyclophosphamide, Fludarabine and Antithymocyte Globulin for Allogeneic Hematopoietic Cell Transplantation in Lower Risk Myelodysplastic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01255319
• Other study ID #: Allo-038
• Status: Recruiting
• Phase: N/A
• First received: November 30, 2010
• Last updated: December 6, 2010
• Start date: November 2010
• Est. completion date: November 2014

Study information

• Verified date: December 2010
• Source: Cooperative Study Group A for Hematology
• Contact: Je-Hwan Lee, Doctor
• Phone: 82-2-3010-3218
• Email: jhlee3[@]amc.seoul.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

To evaluate the feasibility and efficacy of the conditioning regimen with cyclophosphamide, fludarabine and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation (HCT) in patients with lower risk myelodysplastic syndrome (MDS).

Description:

Conditioning therapy

• Cytoxan 50 mg/kg/d on d-3 to -2

• Fludarabine 30 mg/m2 on d-6 to -2

• Antithymocyte globulin (ATG; Thymoglobulin®) 1.5 mg/kg/d (for HLA-matched sibling donor HCT) or 3.0 mg/kg/d (for other alternative donor HCT)

• Methylpd 2 mg/kg/d on d-4 to -1

Mobilization and harvest

• G-CSF 10 mcg/kg/d s.c. on d-3 to 0

• Harvest of PBMCs on d 0 to +1

Donor G PBMC infusion

• Infuse G-PBMCs on d 0 to d+1.

GVHD prophylaxis

• Cyclosporine 1.5 mg/kg i.v. q 12 hrs beginning on d-1 and changed to oral dosing (with twice the i.v. dose) when oral intake is possible. Tapered beginning between d+30 and d+60.

• Methotrexate 15 mg/m2 i.v. on d+2, and 10 mg/m2 i.v. on d+4 and d+7

Preemptive dose-escalating DLIs

• Begin at d+120 or at least 2 wks after IST discontinuation.

• Failure to achieve full donor chimerism No evidence of GVHD

• CD3+ cell dose increment q 4 wks -+ cell dose: HLA-matched donor HCT (1 x 107/kg, 5 x 107/kg, 1 x 108/kg), HLA-matched unrelated donor HCT (1 x 106/kg, 5 x 106/kg, 1 x 107/kg), HLA-matched familial donor HCT (1 x 105/kg, 5 x 105/kg, 1 x 106/kg)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: November 2014
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Patients with lower risk MDS (bone marrow blast percentage < 5%)

• Patients with appropriate hematopoietic cell donor

• Adequate performance status (Karnofsky score of 70 or more; see Appendix II)

• Adequate hepatic and renal function (AST, ALT, and bilirubin < 3.0 x upper normal limit, and creatinine < 2.0 mg/dL).

• Adequate cardiac function (left ventricular ejection fraction of 40% or more on heart scan or echocardiogram)

• Signed and dated informed consent must be obtained from both recipient and donor.

Exclusion Criteria:

• Presence of significant active infection

• Presence of uncontrolled bleeding

• Any coexisting major illness or organ failure

• Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

• Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible

• Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul	Asanbyeongwon-gil, songpa-gu

Sponsors (1)

Lead Sponsor	Collaborator
Cooperative Study Group A for Hematology

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	feasibility and efficacy	To evaluate the feasibility and efficacy of the conditioning regimen with cyclophosphamide, fludarabine and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation (HCT) in patients with lower risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of engraftment and non-relapse mortality (the primary endpoints)	4years	Yes
Secondary	progression-free survival, and overall survival	This study will also evaluate donor chimerism, secondary graft failure, acute and chronic graft-versus-host disease (GVHD), immune recovery, infections, progression-free survival, and overall survival.	4 years	Yes

External Links

•   Conditioning with cyclophosphamide, fludarabine and antithymocyte globulin for allogeneic hematopoietic cell transplantation in lower risk myelodysplastic syndrome