Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents

Asan Medical Center

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Non-malignant Disease; Malignant Disease; Haploidentical Hematopoietic Stem Cell Transplantation

Treatments: Drug: Cyclophosphamide; Radiation: Total body irradiation; Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: Fludarabine; Procedure: TCRαβ-depleted hematopoietic cell transplantation; Device: CliniMACS

Study type: Interventional

Funder types: Other

Identifiers

NCT02014506

AMCPHO-SCT1303

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

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

5. 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

HAPLO

Experimental group

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Radiation: Total body irradiation

Biological: anti-thymocyte globulin

Procedure: TCRαβ-depleted hematopoietic cell transplantation

Biological: filgrastim

Device: CliniMACS