Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Ho Joon Im, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT02014506
First received: December 4, 2013
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Haploidentical Hematopoietic Stem Cell Transplantation
Malignant Disease
Non-malignant Disease
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: anti-thymocyte globulin
Biological: filgrastim
Radiation: Total body irradiation
Procedure: TCRαβ-depleted hematopoietic cell transplantation
Device: CliniMACS
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRαβ-depleted graft [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess engraftment and graft failure [ Time Frame: 28 days posttransplant ] [ Designated as safety issue: Yes ]
  • To estimate the risk of acute GVHD [ Time Frame: 100 days posttransplant ] [ Designated as safety issue: Yes ]
  • To estimate the incidence of relapse [ Time Frame: 100 days and 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • To estimate the incidence and severity of chronic GVHD [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: Yes ]
  • To estimate the overall survival [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: Yes ]
  • To estimate the incidence of bacterial, fungal and viral infection [ Time Frame: 100 days and 1 year posttransplant ] [ Designated as safety issue: Yes ]
  • To estimate the reactivation rate of CMV, EBV [ Time Frame: 100 days and 1 year posttransplant ] [ Designated as safety issue: Yes ]
  • To evaluate the immune reconstitution of T, B, and NK cells [ Time Frame: days 7, 14, 21, 28, 60, 90, 180, 270, and 365 days post-transplant ] [ Designated as safety issue: No ]
  • To evaluate the lineage-specific chimerism using flow cytomery of CD3+, CD19, CD56, TCR αβ, and TCRγδ at pre-transplant [ Time Frame: days 7, 10, 14, 21, 28, 60, 90, 180, 270 and 365 post-transplant ] [ Designated as safety issue: No ]
  • To assess event free survival [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HAPLO Drug: Fludarabine
40mg/M2 once daily IV on days -7 to -2
Drug: Cyclophosphamide
50 mg/kg IV on day -3 and -2
Biological: anti-thymocyte globulin Biological: 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: TCRαβ-depleted hematopoietic cell transplantation Device: CliniMACS
Immunogenetic depletion of TCRαβ cells

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02014506

Contacts
Contact: Ho Joon Im, MD, PhD 82-2-3010-3371 hojim@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Ho Joon Im, MD & PhD    82-2-3010-3371    hojim@amc.seoul.kr   
Principal Investigator: Ho Joon Im, MD & PhD         
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Ho Joon Im, MD, PhD Asan Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Ho Joon Im, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT02014506     History of Changes
Other Study ID Numbers: AMCPHO-SCT1303
Study First Received: December 4, 2013
Last Updated: December 12, 2013
Health Authority: Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
Children and adolescents
Malignant disease
Non-malignant disease
TCRαβ depletion
Haploidentical hematopoietic stem cell transplantation

Additional relevant MeSH terms:
Cyclophosphamide
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 22, 2014