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Closed due to slow accrual. Nine subjects enrolled over 7 years.
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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.
The study is being conducted to assess the following:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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). |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| unrelated BM with T cell depletion | Biological | Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3 | Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Veno-occlusive Disease (VOD) - Moderate and Severe | 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 | 100 days |
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:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Neena Kapoor, M.D. | Children's Hospital Los Angeles, University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Unrelated BM With T Cell Depletion | 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. unrelated BM with T cell depletion: Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted). |
| FG001 | Unrelated Cord Blood | 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). unrelated cord blood: Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP. |
| FG002 | Haplo BM With T Cell Depletion | If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. haplo BM with T cell depletion: haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. |
| FG003 | Unrelated PBSC With T Cell Depletion | 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. unrelated PBSC with T cell depletion: peripheral blood stem cell will be processed for CD34+ cell isolation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Unrelated BM With T Cell Depletion | 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. unrelated BM with T cell depletion: Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 100 day |
|
Adverse event data was collected over a period of 1 year post transplant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Unrelated BM With T Cell Depletion | 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. unrelated BM with T cell depletion: Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinusoidal obstruction syndrome | Hepatobiliary disorders | SOS | Systematic Assessment | Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease (VOD), is a distinctive and potentially fatal form of hepatic injury that occurs predominantly, if not only, after drug or toxin exposure |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Graft Versus Host Disease | Skin and subcutaneous tissue disorders | Systematic Assessment | Graft versus host disease - condition post transplant the donor's immune cells in the transplant (graft) make antibodies against the patient's tissues (host) and attack vital organs (skin, GI track and liver common organs attacked) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neena Kapoor, M.D. | Children's Hospital Los Angeles | 323-361-2546 | nkapoor@chla.usc.edu |
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| ID | Term |
|---|---|
| D016511 | Severe Combined Immunodeficiency |
| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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|
| unrelated cord blood | Biological | Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP. |
|
|
| haplo BM with T cell depletion | Biological | haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. |
|
|
| unrelated PBSC with T cell depletion | Device | peripheral blood stem cell will be processed for CD34+ cell isolation. |
|
|
| Number of Participants With Graft Versus Host Disease (GVHD) - Grade III or IV |
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. |
| 1 year |
| Overall Survival | Overalls survival of patient at 1 year post transplant | 1 year |
| Unrelated Cord Blood |
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). unrelated cord blood: Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP. |
| BG002 | Haplo BM With T Cell Depletion | If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. haplo BM with T cell depletion: haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. |
| BG003 | Unrelated PBSC With T Cell Depletion | 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. unrelated PBSC with T cell depletion: peripheral blood stem cell will be processed for CD34+ cell isolation. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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).
unrelated cord blood: Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.
| OG002 | Haplo BM With T Cell Depletion | If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. haplo BM with T cell depletion: haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. |
| OG003 | Unrelated PBSC With T Cell Depletion | 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. unrelated PBSC with T cell depletion: peripheral blood stem cell will be processed for CD34+ cell isolation. |
|
|
| Secondary | Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3 | Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Other Pre-specified | Number of Participants With Veno-occlusive Disease (VOD) - Moderate and Severe | 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 | Posted | Count of Participants | Participants | 100 days |
|
|
|
| Other Pre-specified | Number of Participants With Graft Versus Host Disease (GVHD) - Grade III or IV | 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. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Other Pre-specified | Overall Survival | Overalls survival of patient at 1 year post transplant | Posted | Count of Participants | Participants | 1 year |
|
|
|
| 1 |
| 7 |
| 1 |
| 7 |
| 5 |
| 7 |
| EG001 | Unrelated Cord Blood | 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). unrelated cord blood: Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP. | 1 | 2 | 1 | 2 | 1 | 2 |
| EG002 | Haplo BM With T Cell Depletion | If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. haplo BM with T cell depletion: haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG003 | Unrelated PBSC With T Cell Depletion | 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. unrelated PBSC with T cell depletion: peripheral blood stem cell will be processed for CD34+ cell isolation. | 0 | 0 | 0 | 0 | 0 | 0 |
|
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| Infection - Aspergillis | Infections and infestations | Systematic Assessment | Pulmonary Aspergillis infection |
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| Infection - Fungal | Infections and infestations | Systematic Assessment | Pulmonary fungal infection |
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| Pulmonary Hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Seizure | Nervous system disorders | Systematic Assessment | Busulfan toxicity |
|
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| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |