Back to results

SCID Bu/Flu/ATG Study With T Cell Depletion

Primary Purpose

Severe Combined Immunodeficiency

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

unrelated BM with T cell depletion

unrelated cord blood

haplo BM with T cell depletion

unrelated PBSC with T cell depletion

About this trial

This is an interventional treatment trial for Severe Combined Immunodeficiency focused on measuring 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

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
1. Renal: creatinine clearance or GFR ≥50 ml/min/1.73m2, and not requiring dialysis
2. 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.
3. Infectious disease status. The presence of infection per se will not be a reason for exclusion from the study. Patients with SCID are frequently infected with both routine pathogens as well as opportunistic infections. Antibiotic, antifungal and antiviral prophylaxis and therapy will be instituted as clinically indicated. Despite the use of antimicrobial therapy, the ability to control infections will not be achieved unless HSCT is performed. Therefore, subjects may be enrolled in the study, even though infection is present, because control of infection may depend on engraftment of a donor immune system.
4. Patients will be 0-21 years of age.

Exclusion Criteria:

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.

Sites / Locations

Children's Hospital Los Angeles

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Arm Label

unrelated BM with T cell depletion

unrelated cord blood

haplo BM with T cell depletion

unrelated PBSC with T cell depletion

Arm Description

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.

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).

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects.

Full Information

NCT ID

NCT02127892

First Posted

October 19, 2012

Last Updated

August 18, 2017

Sponsor

Neena Kapoor, M.D.

1. Study Identification

Unique Protocol Identification Number

NCT02127892

Brief Title

SCID Bu/Flu/ATG Study With T Cell Depletion

Official Title

Phase I/II Trial of Hematopoietic Stem Cell Transplant (HSCT) for Children With Severe Combined Immune Deficiency (SCID) and Without an HLA-Matched Sibling Donor

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Terminated

Why Stopped

Closed due to slow accrual. Nine subjects enrolled over 7 years.

Study Start Date

January 2, 2007 (Actual)

Primary Completion Date

August 1, 2016 (Actual)

Study Completion Date

August 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Neena Kapoor, M.D.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The study is being conducted to assess the following: overall survival event-free survival (events are defined as: death,non-engraftment/2nd transplant, immune reconstitution failure) acute toxicity of the conditioning regimen engraftment frequency immune reconstitution frequency and tempo acute and chronic graft-versus-host disease (GVHD), frequency and severity. The outcome from this protocol will be compared to the retrospective cohort consisting of all patients who have undergone haplo-identical HSCT for SCID at CHLA from 1984-2006 based on the assessment of the above-listed endpoints. The CliniMACS device will be used for CD34+ selection in place of the Isolex 300i. The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

unrelated BM with T cell depletion

Arm Type

Other

Arm Description

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.

Arm Title

unrelated cord blood

Arm Type

Other

Arm Description

Arm Title

haplo BM with T cell depletion

Arm Type

Other

Arm Description

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

Arm Title

unrelated PBSC with T cell depletion

Arm Type

Other

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

unrelated BM with T cell depletion

Other Intervention Name(s)

CD34+ selection using CliniMACS

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

unrelated cord blood

Other Intervention Name(s)

umbilical cord blood

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

haplo BM with T cell depletion

Other Intervention Name(s)

CD34+ selection with CliniMACS

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

unrelated PBSC with T cell depletion

Other Intervention Name(s)

CD34+ selection using CliniMACS

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Engraftment

Description

Time Frame

100 day

Secondary Outcome Measure Information:

Title

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

Description

Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects.

Time Frame

1 year

Other Pre-specified Outcome Measures:

Title

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

Description

Evaluation of veno-occlusive disease determined by the presence of the following features; fluid retention, weight gain, leaky capillary syndrome, painful liver enlargement, refractoriness to platelet tranfusion and hyperbilirubinemia

Time Frame

100 days

Title

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

Description

GVHD disease surveillance done by clinical evaluation, to include history, physical examination, specifically for rash, jaundice, liver dysfunction, nausea and vomiting, diarrhea and failure to thrive.

Time Frame

1 year

Title

Overall Survival

Description

Overalls survival of patient at 1 year post transplant

Time Frame

1 year

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Infectious disease status. The presence of infection per se will not be a reason for exclusion from the study. Patients with SCID are frequently infected with both routine pathogens as well as opportunistic infections. Antibiotic, antifungal and antiviral prophylaxis and therapy will be instituted as clinically indicated. Despite the use of antimicrobial therapy, the ability to control infections will not be achieved unless HSCT is performed. Therefore, subjects may be enrolled in the study, even though infection is present, because control of infection may depend on engraftment of a donor immune system. Patients will be 0-21 years of age. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Neena Kapoor, M.D.

Organizational Affiliation

Children's Hospital Los Angeles, University of Southern California

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital Los Angeles

City

Los Angeles

State/Province

California

ZIP/Postal Code

90027

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

SCID Bu/Flu/ATG Study With T Cell Depletion

We'll reach out to this number within 24 hrs