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

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Marrow Failure Syndromes; Immunodeficiencies; Immune Dysregulation Syndromes
• Intervention / Treatment: Device: CliniMACs device

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 22 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bone Marrow Failure Syndrome; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.	Device: CliniMACs device; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Experimental: Immunodeficiency / Dysregulation; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.	Device: CliniMACs device; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Nancy Bunin, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimate): October 29, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: March 16, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Graft versus host disease; Transplant related mortality; Bone marrow transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Bone Marrow Diseases; Hematologic Diseases; Syndrome; Bone Marrow Failure Disorders; Pancytopenia
• Other Study ID Numbers: 11-008330; CHP 980 (Other Identifier: Children's Hospital of Philadelphia)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No