Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents

Haploidentical Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02014506
• Other study ID #: AMCPHO-SCT1303
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 4, 2013
• Last updated: March 24, 2017
• Start date: January 2017
• Est. completion date: December 2018

Study information

• Verified date: March 2017
• Source: Asan Medical Center
• Contact: Ho Joon Im, MD, PhD
• Phone: 82-2-3010-3371
• Email: hojim[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose of study: This phase I/II trial is to evaluate the safety and feasibility of TCRαβ-depleted graft from haploidentical family donors in treating children and adolescents with malignant or non-malignant diseases.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

A. Disease inclusions

1. Hematologic malignancy:

• Acute lymphoblastic leukemia including induction failure, CR1 (Ph+, t(4:11), hypodiploid and other very high risk features), = CR2, infant ALL with MLL or other unfavorable features

• Acute myeloid leukemia excluding CR1 with t(8:21), inv(16), t(15:17), and Down syndrome

• Myelodysplastic syndrome: RCC with -7 or RCC in need of transfusion

• Chronic myeloid leukemia in AP

• Juvenile myelomonocytic leukemia

• Malignant lymphoma, NHL or HD, after failed autologous HSCT

• Other

2. Non-hematologic malignancy

• Relapsed or refractory solid tumors including neuroblastoma, rhabdomyosarcoma and so on

3. Non-malignant hematologic disease

• Acquired severe and very severe aplastic anemia

• Fanconi anemia

• Paroxysmal nocturnal hemoglobinuria

• Congenital dyserythropoietic anemia

• Others

4. Inherited or metabolic disease

• Hemophagocytic lymphohistiocytosis

• Malignant osteopetrosis

• Storage diseases

• Others B. Recipient inclusions

1. Age < 21 years 2. No HLA-identical stem cell donor available 3. Lansky-Play performance score >60 4. No active infection at the time of transplantation

Exclusion Criteria:

1. HIV-infection

2. Presence of active and serious infection

3. Cardiac ejection fraction <35% on echocardiography

4. Severe pulmonary dysfunction (DLCO <30%)

5. Liver function abnormalities with bilirubin >4mg/dL and elevation of transaminases > 400U/L

6. Concurrent severe or uncontrolled medical disease

7. Patients who are pregnant

8. Patients unwilling or unable to comply with the protocol or unable to give informed consent

Related Conditions & MeSH terms

• Haploidentical Hematopoietic Stem Cell Transplantation
• Malignant Disease
• Non-malignant Disease

Intervention

Drug:
• Fludarabine
40mg/M2 once daily IV on days -7 to -2
• Cyclophosphamide
50 mg/kg IV on day -3 and -2

Biological:
• anti-thymocyte globulin

• filgrastim
Beginning on day 4 and continuing until blood counts recover

Radiation:
• Total body irradiation
200 cGy per day on D-6 to -4 (eligible disease except aplastic anemia) 200 cGy per day on D-5 & -4 (severe aplastic anemia)

Procedure:
• TCRaß-depleted hematopoietic cell transplantation

Device:
• CliniMACS
Immunogenetic depletion of TCRaß cells

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 (3)

Im HJ, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, Chi HS, Seo JJ. Excellent outcome of haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia. Biol Blood Marrow Transplant. 2013 May;19(5):754-9. doi: 10.1016/j.bbmt.2013.01.023. — View Citation

Park JA, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ, Im HJ. Successful rescue of early graft failure in pediatric patients using T-cell-depleted haploidentical hematopoietic SCT. Bone Marrow Transplant. 2014 Feb;49(2):270-5. doi: 10.1038/bmt.2013.163. — View Citation

Schumm M, Lang P, Bethge W, Faul C, Feuchtinger T, Pfeiffer M, Vogel W, Huppert V, Handgretinger R. Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device. Cytotherapy. 2013 Oct;15(10):1253-8. doi: 10.1016/j.jcyt.2013.05.014. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRaß-depleted graft		1 year posttransplant
Secondary	To assess engraftment and graft failure		28 days posttransplant
Secondary	To estimate the risk of acute GVHD		100 days posttransplant
Secondary	To estimate the incidence of relapse		100 days and 1 year post-transplant
Secondary	To estimate the incidence and severity of chronic GVHD		1 year posttransplant
Secondary	To estimate the overall survival		1 year posttransplant
Secondary	To estimate the incidence of bacterial, fungal and viral infection		100 days and 1 year posttransplant
Secondary	To estimate the reactivation rate of CMV, EBV		100 days and 1 year posttransplant
Secondary	To evaluate the immune reconstitution of T, B, and NK cells		days 7, 14, 21, 28, 60, 90, 180, 270, and 365 days post-transplant
Secondary	To evaluate the lineage-specific chimerism using flow cytomery of CD3+, CD19, CD56, TCR aß, and TCR?d at pre-transplant		days 7, 10, 14, 21, 28, 60, 90, 180, 270 and 365 post-transplant
Secondary	To assess event free survival		1 year posttransplant

External Links

•   cyclophosphamide
•   fludarabine
•   leukemia
•   Stem cell transplant
•   stem cell transplantation