Study of Fludarabine + Cyclophosphamide + TBI Conditioning Regimen for Double Units Cord Blood Transplantation(CBT)in Severe Aplastic Anemia(SAA)

Phase I/II Study of Fludarabine, Cyclophosphamide Plus TBI Conditioning Regimen for Double Units Cord Blood Transplantation in Severe Aplastic Anemia

Severe aplastic anemia is a fatal disease and patients without HLA matched siblings need alternative treatment option. Cord blood transplantation (CBT) has become an alternative treatment means in various diseases, but it has not been proved to be good for severe aplastic anemia. Double units CBT is proposed to have better engraftment potential and and we reported successful double units UCBT after engraftment failure with single unit with promising result. To increase the engraftment potential, fludarabine, cyclophosphamide plus TBI conditioning regimen for double units cord blood transplantation was proposed for the patient with severe aplastic anemia without HLA-matched donor.

Study Overview

• Status: Unknown
• Conditions: Aplastic Anemia
• Intervention / Treatment: Other: Cyclophosphosphamide, TBI

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Recruiting
    • Seoul National University Hospital
    • Contact: Hyo Seop Ahn, M.D, Ph.D; Phone Number: 82 2 2072 3625; Email: hsahn@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion.

• Peripheral blood

  • Neutrophils < 0.5 x 109/l
  • Platelets < 20 x 109/l
  • Corrected reticulocytes < 1%

• Bone marrow

  • Severe hypocellularity (< 25%)
  • Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells
• No prior hematopoietic stem cell transplantation.
• Age: no limits.
• Performance status: ECOG 0-2.

• Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases.

  • Heart: a shortening fraction > 30%, ejection fraction > 45%.
  • Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
  • Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.
• Patients must lack any active viral infections or active fungal infection.
• No appropriate donor
• Appropriate cord blood is available: matched at least in 4/6 of A, B, DR loci.
• Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria:

• Pregnant or nursing women.
• Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
• Psychiatric disorder that would preclude compliance.
• Congenital aplastic anemia including Fanconi anemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fludarabine	Other: Cyclophosphosphamide, TBI; fludarabine (30 mg/m2 once daily i.v. on days -7, -6, -5, -4, -3, & -2) (if body weight < 10 kg or if age < 1 year: 1.33 mg/kg) cyclophosphamide (60 mg/kg once daily i.v. on days -9, & -8) total body irradiation (3G on days -1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for cord blood transplantation (CBT) in severe aplastic anemia.	From Oct 2008. to Sep 2011

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the incidence and severity of toxicity and treatment related mortality	From Oct 2008. to Sep 2011
To evaluate overall and event free survival rate	From Oct 2008. to Sep 2011
To evaluate acute and chronic GVHD	From Oct 2008. to Sep 2011
To evaluate immunologic recovery after CBT	From Oct 2008. to Sep 2011

Collaborators and Investigators

• Sponsor: The Korean Society of Pediatric Hematology Oncology

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): September 1, 2012

Study Registration Dates

• First Submitted: April 14, 2009
• First Submitted That Met QC Criteria: April 14, 2009
• First Posted (Estimate): April 15, 2009

Study Record Updates

• Last Update Posted (Estimate): March 26, 2012
• Last Update Submitted That Met QC Criteria: March 23, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Fludarabine, Cyclophosphamide, TBI, severe aplastic anemia,; cord blood transplantation, pediatric
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: KSPHO-SCT0804