Clinical trial NCT01255319: Cyclophosphamide, Fludarabine and Antithymocyte Globulin Conditioning in Myelodysplastic Syndrome (MDS)
Official title: Conditioning With Cyclophosphamide, Fludarabine and Antithymocyte Globulin for Allogeneic Hematopoietic Cell Transplantation in Lower Risk Myelodysplastic Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myelodysplastic Syndrome
Keywords: MDS
Lead sponsor: Cooperative Study Group A for Hematology
Sponsor class: NETWORK
First posted: 2010-12-07
Enrollment: 15
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with lower risk MDS

Brief 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).

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)

Eligibility criteria: 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

Primary outcomes:
measure: feasibility and efficacy
timeFrame: 4years
Secondary outcomes:
measure: progression-free survival, and overall survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Asanbyeongwon-gil, songpa-gu
Study officials:
affiliation: Asan Medical Center
name: Je-Hwan Lee, Doctor
role: PRINCIPAL_INVESTIGATOR
References: