HLA-haploidentical Hematopoietic Stem Cell Transplantation for Children and Adolescents With Acute Leukemia, Myelodysplastic Syndrome and Solid Tumors

Solid Tumors Clinical Trial

Official title:

HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3 Depletion for Children and Adolescents With Acute Leukemia, Myelodysplastic Syndrome and Solid Tumors After Conditioning of TBI, Fludarabine, Cyclophosphamide and Antithymocyte Globulin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01509300
• Other study ID #: AMCPHO-SCT0902
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: January 5, 2012
• Last updated: January 12, 2012
• Start date: January 2012
• Est. completion date: March 2014

Study information

• Verified date: January 2012
• Source: Asan Medical Center
• Contact: Ho Joon Im, MD & PhD
• Phone: 82-2-3010-3371
• Email: hojim[@]amc.seoul.kr
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Conditioning with total body irradiation (TBI) and fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, T-cell depletion may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.

PURPOSE: This phase I/II trial is to evaluate the safety and efficacy of TBI, fludarabine, cyclophosphamide and antithymocyte globulin with T-cell depleted graft from haploidentical donors in treating patients with acute leukemia and myelodysplastic syndrome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria

1. Disease characteristics

• Acute lymphoblastic leukemia (first remission, high risk; beyond first remission; refractory)

• Acute myeloblastic leukemia (first remission, high risk; beyond first remission; refractory)

• Myelodysplastic syndrome

• Solid tumors (Refractory/relapse)

2. No HLA-identical family member or closely matched (8 or 7 of 8 HLA-locus match) unrelated marrow donor available

3. HLA-haploidentical related donor available

Exclusion criteria

1. Active fungal infections

2. HIV positive

3. Pregnant or nursing

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Solid Tumors
• Syndrome

Intervention

Biological:
• anti-thymocyte globulin
On days -10 to -9
• filgrastim
Beginning on day 4 and continuing until blood counts recover

Radiation:
• Total body irradiation
2Gy D-6 to D-4

Drug:
• Fludarabine
30mg/M2 once daily IV on days -8 to -4
• cyclophosphamide
60 mg/kg IV on day-3 and -2
• Tacrolimus
begin on 0
• Mycophenolate mofetil
begin on 0
• Rituximab
375mg/m2 on day +21

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. — View Citation

Lang P, Handgretinger R. Haploidentical SCT in children: an update and future perspectives. Bone Marrow Transplant. 2008 Oct;42 Suppl 2:S54-9. doi: 10.1038/bmt.2008.285. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplantation-related mortality and overall survival of TBI, Fludarabine, Cyclophosphamide and anti-thymocyte globulin for engraftment of CD3 depleted haploidentical peripheral blood stem cells.		2 years post-transplant	Yes
Secondary	Engraftment and graft failure rates	Number of patients who failed to stable engraftment by 28 days	28 days engraftment and graft failure	Yes
Secondary	Incidence of acute GVHD	Number of patients with acute GVHD.	100 days post-transplant	Yes
Secondary	Treatment related mortality	Number of death after transplantation	100 days post-transplant	Yes
Secondary	Relapse rate and overall survival		2 year after transplantation	No