Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases

Immunodeficiencies Clinical Trial

— MiniClini  

Official title:

Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02277639
• Other study ID #: 11-008330
• Secondary ID: CHP 980
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2014
• Last updated: March 16, 2018
• Start date: November 2011
• Est. completion date: March 2016

Study information

• Verified date: March 2018
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.

Description:

This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states.

Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

Inclusion Criteria:

• Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia

• Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease

• Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy

• Organ function clearance

Exclusion Criteria:

• Uncontrolled bacterial, viral or fungal infections

• HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.

• Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes

• Pregnant Females

Related Conditions & MeSH terms

• Anemia, Aplastic
• Bone Marrow Failure Syndromes
• Hemoglobinuria, Paroxysmal
• Immune Dysregulation Syndromes
• Immunodeficiencies
• Immunologic Deficiency Syndromes
• Pancytopenia
• Syndrome

Intervention

Device:
• CliniMACs device
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Engraftment	The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.	One Year