SCID Bu/Flu/ATG Study With T Cell Depletion

NCT02127892 | Terminated Phase 1 Results DMC FDA Device

• 1 other identifier: CCI-06-00243
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD), 2) unrelated cord blood donor, or 3) a haplo-identical (parental) donor (in descending order of preference).Patients will receive a novel conditioning regimen with Busulfan, Fludarabine and Anti-thymocyte globulin (ATG) followed by an unrelated donor hematopoietic stem cell transplant (HSCT) with T-cell depletion using the CliniMACS device.

Conditions

Severe Combined Immunodeficiency

Keywords

Severe Combined Immune Deficiency; SCID; HLA-matched unrelated donor; unrelated; MUD; bone marrow; cord blood; haplo-identical; peripheral blood; CD34+ selection; T cell depletion; HSCT; BMT; CliniMACS

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Engraftment

  Engraftment is defined as recovery of blood counts (neutrophil and platelet engraftment) with cells of donor origin, documented by either bone marrow or peripheral blood chimerism assays after hematopoietic stem cell transplant.

  100 day

Secondary Outcomes (1)

• Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3

  1 year

Other Outcomes (3)

• Number of Participants With Veno-occlusive Disease (VOD) - Moderate and Severe

  100 days

• Number of Participants With Graft Versus Host Disease (GVHD) - Grade III or IV

  1 year

• Overall Survival

  1 year

Study Arms (4)

unrelated BM with T cell depletion

OTHER

Acceptable matching for matched unrelated donor (MUD) bone marrow will be genotypic matches at 10 of 10 HLA alleles (HLA-A, B, C, DR and DQ) or 9 of 10 HLA alleles.

Biological: unrelated BM with T cell depletion

unrelated cord blood

OTHER

Acceptable matching for unrelated cord blood will be a genotypic match at 6 of 6 alleles (HLA A, B and DR) or 5 of 6 alleles, but not with mismatches at both alleles of a single locus (e.g. not mismatched for both HLA A alleles).

Biological: unrelated cord blood

haplo BM with T cell depletion

OTHER

If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors.

Biological: haplo BM with T cell depletion

unrelated PBSC with T cell depletion

OTHER

The preferred source will be bone marrow, however, if a donor is unable or unwilling to donate bone marrow, peripheral blood stem cells (PBSC) will be allowed.

Device: unrelated PBSC with T cell depletion

Interventions

unrelated BM with T cell depletion BIOLOGICAL

Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).

Also known as: CD34+ selection using CliniMACS

unrelated BM with T cell depletion

unrelated cord blood BIOLOGICAL

Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.

Also known as: umbilical cord blood

unrelated cord blood

haplo BM with T cell depletion BIOLOGICAL

haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.

Also known as: CD34+ selection with CliniMACS

haplo BM with T cell depletion

unrelated PBSC with T cell depletion DEVICE

peripheral blood stem cell will be processed for CD34+ cell isolation.

Also known as: CD34+ selection using CliniMACS

unrelated PBSC with T cell depletion

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All patients with SCID who lack a histocompatible sibling or HLA-matched related donor will be considered as candidates for this study protocol.
• Eligible patients must have adequate physical function to tolerate the chemotherapy conditioning regimen and the HSCT, as measure by:
• Renal: creatinine clearance or GFR ≥50 ml/min/1.73m2, and not requiring dialysis
• Pulmonary: Because patients with SCID frequently present with infectious pneumonia causing ventilatory failure, patients will be considered for enrollment in the study even if respiratory failure requiring mechanical ventilatory support is present. In patients recently diagnosed with pneumonia, efforts to stabilize the respiratory status will be made prior to enrollment in the study.
• Patients will be 0-21 years of age.

You may not qualify if:

• Patient with histocompatible sibling or other related donor
• End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning.
• Renal failure requiring dialysis
• Congenital heart disease resulting in congestive heart failure
• Severe CNS disease, e.g., coma or intractable seizures
• Ventilatory failure due to non-infectious etiology
• Major congenital anomalies that adversely affect survival, eg CNS malformations
• Metabolic diseases that would affect transplant survival, eg urea cycle disorders
• HIV infection
• Since the only chance of survival for patients with SCID is successful transplantation, all patients with SCID will be considered to be potential subjects for the study, regardless of end-organ dysfunction.

Sponsors & Collaborators

• Neena Kapoor, M.D.: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Severe Combined Immunodeficiency

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Neena Kapoor, M.D.
• Organization: Children's Hospital Los Angeles

nkapoor@chla.usc.edu

323-361-2546

Study Officials

• Neena Kapoor, M.D.

  Children's Hospital Los Angeles, University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics, Keck School of Medicine; Division Head, Division of Research Immunology/BMT

Study Record Dates

• First Submitted: October 19, 2012
• First Posted: May 1, 2014
• Study Start: January 2, 2007
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 18, 2017
• Results First Posted: September 18, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)