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

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

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).

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndrome

Detailed 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)

• Study Type: Observational
• Enrollment (Anticipated): 15

Contacts and Locations

Study Locations

• Korea, Republic of
  • Asanbyeongwon-gil, songpa-gu
    • Seoul, Asanbyeongwon-gil, songpa-gu, Korea, Republic of, 138-736
      • Recruiting
      • Asan Medical Center
      • Contact: Yae-Eun Jang, nurse; Phone Number: 82-2-3010-6378; Email: redpin75@paran.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with lower risk MDS

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Cooperative Study Group A for Hematology
• Investigators: Principal Investigator: Je-Hwan Lee, Doctor, Asan Medical Center

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): November 1, 2012
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: November 30, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (Estimate): December 7, 2010

Study Record Updates

• Last Update Posted (Estimate): December 7, 2010
• Last Update Submitted That Met QC Criteria: December 6, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: MDS
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: Allo-038