Adenosine Deaminase Deficiency, Severe Combined Immunodeficiencies (SCID)
Conditions
Keywords
Gene therapy, Hematopoietic stem and progenitor cells, Lentiviral vector, ADA-SCID
Brief summary
This is a historically controlled, non-randomized Phase I/II clinical trial to assess the safety and efficacy of autologous transplantation of CD34+ hematopoietic stem/progenitor cells (HSPCs), obtained from infants affected by ADA-SCID, following transduction of the HSPCs with a lentiviral vector (LV) carrying the human ADA complementary DNA (cDNA) under the control of the elongation factor 1 alpha shortened (EFS) promoter. Subjects treated in the trial receive the infusion of autologous, transduced cells following marrow cytoreduction with busulfan. The outcomes are compared to those observed in a historical control group of patients who received an allogeneic hematopoietic stem cell transplant (HSCT). This Phase I/II clinical trial will be performed at Great Ormond Street Hospital (GOSH), London, United Kingdom.
Interventions
GENETICInfusion of autologous EFS-ADA LV CD34+ cells
Autologous EFS-ADA LV CD34+ cells (OTL-101\*) are infused intravenously
OTHERHaematopoietic Stem Cell Transplantation (HSCT)
Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from GOSH will be collected as comparator group.
DRUGBusulfan
Busulfan is used for non-myeloablative conditioning
DRUGPeg-Ada
Peg-Ada enzyme replacement therapy is discontinued at Day +3- (-3/+15 days) after successful engraftment
Sponsors
Orchard Therapeutics
Great Ormond Street Hospital for Children NHS Foundation Trust
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 15 Years
Healthy volunteers
No
Inclusion criteria
Gene Therapy (On Trial) Inclusion Criteria: 1. Diagnosis of ADA-SCID confirmed by DNA sequencing or by confirmed absence of \<3% of ADA enzymatic activity in peripheral blood (or for neonates) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of Polyethylene glycol-modified ADA (PEG-ADA) replacement therapy 2. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor 3. Patients (male or female) \<5 years of age OR Patients (male or female) ≥ 5 years to 15 years of age who have preserved thymic function as evidenced by presence of \>10 % naïve T cells (CD4+45RA+27+ cells) 4. Parental/guardian signed informed consent
Exclusion criteria
1. Cytogenetic abnormalities on peripheral blood 2. Evidence of active malignant disease 3. Known sensitivity to busulfan 4. If applicable, confirmed pregnancy (to be tested in patients above 12 years old) Gene Therapy (CUP) A group of patients were treated under CUP (GOSH special license) either because the study was not yet open and patients needed urgent treatment, or because they were outside of the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Vector Integration Into Known Protooncogenes (3 Years) | 36 months | Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent \>30% of the total integration sites detected. There were no instances of clonal proliferation in the course of the 36 month follow-up for on-study and CUP subjects; hence, a detailed analysis of the frequency of clonal expansion associated with vector integration near proto-oncogenes was not generated. |
| Change From Baseline in CD3+ T Cell Counts (3 Years) | 36 months | Immune reconstitution was assessed by change in CD3+ T Cell counts over time. |
| ADA Activity in Erythrocytes | 36 months | ADA enzyme activity was assessed as a measure of successful engraftment of genetically modified Hematopoietic stem progenitor cells (HSPCs), as it marks sustained gene expression from the normal ADA transgene. |
| Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 36 months | Decreased dATP levels coincide with increased ADA enzyme activity, detoxification was used as a marker of correction of the defective ADA gene. The threshold for detoxification was \<100 μmol/L. |
| Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 12 months | Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101\* or HSCT |
| Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 12 months | Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death. |
| Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils) | 36 months | Engraftment of transduced cells was assessed using vector gene marking in granulocytes (neutrophils) |
| VCN in Peripheral Blood Mononuclear Cells (PBMCs) | 36 months | Engraftment of transduced cells was assessed using vector gene marking in PBMCs |
| VCN in CD3+ T Cells | 36 months | Engraftment of transduced cells was assessed using vector gene marking |
| VCN in CD19+ B Cells | 36 months | Engraftment of transduced cells was assessed using vector gene marking in CD19+ B Cells |
| Change From Baseline in CD3+ T Cell Counts (1 Year) | 12 months | Immune reconstitution was assessed by change in CD3+ T Cell counts over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 36 months | Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death. |
| Infection Rate | 36 months | The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. |
| OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 36 months | Overall survival (OS) is defined as the percentage of subjects alive at 36 months post- treatment with OTL-101\* or HSCT |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gene Therapy The safety population consists of all OTL-101\*-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101\*-treated subjects (on-study and CUP). | 20 |
| Historical Control Group Complete HSCT historical control group consisting of ADA-SCID patients with any type of donor treated with HSCT at GOSH from 2000 to 2016 (referred to as the All HSCT Controls group) | 16 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Treatment Failure | 1 | 0 |
Baseline characteristics
| Characteristic | Gene Therapy | Historical Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 16 Participants | 36 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity, n Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity, n Not reported | 0 Participants | 16 Participants | 16 Participants |
| Race/Ethnicity, Customized Ethnicity, n Other | 6 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity, n Unknown | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity, n White European | 10 Participants | 0 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 20 participants | 16 participants | 36 participants |
| Sex/Gender, Customized Sex, n Female | 8 Participants | 0 Participants | 8 Participants |
| Sex/Gender, Customized Sex, n Male | 12 Participants | 0 Participants | 12 Participants |
| Sex/Gender, Customized Sex, n Not Reported | 0 Participants | 16 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 20 / 20 | 10 / 10 |
| serious Total, serious adverse events | 11 / 20 | 7 / 10 |
Outcome results
Primary
ADA Activity in Erythrocytes
ADA enzyme activity was assessed as a measure of successful engraftment of genetically modified Hematopoietic stem progenitor cells (HSPCs), as it marks sustained gene expression from the normal ADA transgene.
Time frame: 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | ADA Activity in Erythrocytes | 638.0 nmol/h/mg |
| OTL-101* On-Study and CUP Subjects | ADA Activity in Erythrocytes | 490.5 nmol/h/mg |
| HSCT Controls Without MRD | ADA Activity in Erythrocytes | 86.5 nmol/h/mg |
| HSCT Controls With MRD | ADA Activity in Erythrocytes | 1.0 nmol/h/mg |
| All HSCT Controls | ADA Activity in Erythrocytes | 23.0 nmol/h/mg |
Primary
Change From Baseline in CD3+ T Cell Counts (1 Year)
Immune reconstitution was assessed by change in CD3+ T Cell counts over time.
Time frame: 12 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as CD3+ T cell count data was not collected due to the historical nature of the population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| OTL-101* On-Study Subjects | Change From Baseline in CD3+ T Cell Counts (1 Year) | 3.58 10e9 cells/L |
| OTL-101* On-Study and CUP Subjects | Change From Baseline in CD3+ T Cell Counts (1 Year) | 3.18 10e9 cells/L |
Comparison: Mixed-Effect Model Repeated Measure (MMRM) Analysis of Change from Baseline to Month 12 in Log-Transformed CD3+ T Cell count (OTL-101\*) for OTL-101\* on-study subjects group.p-value: =0.002Mixed Models Analysis
Comparison: MMRM Analysis of Change from Baseline to Month 12 in Log-Transformed CD3+ T Cell count (OTL-101\*) for OTL-101\* on-study and CUP subjects group.p-value: <0.001Mixed Models Analysis
Primary
Change From Baseline in CD3+ T Cell Counts (3 Years)
Immune reconstitution was assessed by change in CD3+ T Cell counts over time.
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as CD3+ T cell count data was not collected due to the historical nature of the population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | Change From Baseline in CD3+ T Cell Counts (3 Years) | 1.060 10e9 cells/L |
| OTL-101* On-Study and CUP Subjects | Change From Baseline in CD3+ T Cell Counts (3 Years) | 1.090 10e9 cells/L |
Primary
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| OTL-101* On-Study and CUP Subjects | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls Without MRD | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls With MRD | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| All HSCT Controls | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.
Primary
Frequency of Vector Integration Into Known Protooncogenes (3 Years)
Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent \>30% of the total integration sites detected. There were no instances of clonal proliferation in the course of the 36 month follow-up for on-study and CUP subjects; hence, a detailed analysis of the frequency of clonal expansion associated with vector integration near proto-oncogenes was not generated.
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VISA is not relevant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | Frequency of Vector Integration Into Known Protooncogenes (3 Years) | 0 % of integration in known protooncogenes |
| OTL-101* On-Study and CUP Subjects | Frequency of Vector Integration Into Known Protooncogenes (3 Years) | 0 % of integration in known protooncogenes |
Primary
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101\* or HSCT
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| OTL-101* On-Study and CUP Subjects | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls Without MRD | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls With MRD | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| All HSCT Controls | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of patients alive at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of patients alive at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (all historical controls) were compared to the percentage of patients alive at 1-year post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.
Primary
Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes
Decreased dATP levels coincide with increased ADA enzyme activity, detoxification was used as a marker of correction of the defective ADA gene. The threshold for detoxification was \<100 μmol/L.
Time frame: 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 50.0 umol/L |
| OTL-101* On-Study and CUP Subjects | Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 50.0 umol/L |
| HSCT Controls Without MRD | Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 0.0 umol/L |
| HSCT Controls With MRD | Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 114.0 umol/L |
| All HSCT Controls | Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes | 90.0 umol/L |
Primary
VCN in CD19+ B Cells
Engraftment of transduced cells was assessed using vector gene marking in CD19+ B Cells
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | VCN in CD19+ B Cells | 0.880 copies/cell |
| OTL-101* On-Study and CUP Subjects | VCN in CD19+ B Cells | 1.190 copies/cell |
Primary
VCN in CD3+ T Cells
Engraftment of transduced cells was assessed using vector gene marking
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | VCN in CD3+ T Cells | 1.065 copies/cell |
| OTL-101* On-Study and CUP Subjects | VCN in CD3+ T Cells | 1.160 copies/cell |
Primary
VCN in Peripheral Blood Mononuclear Cells (PBMCs)
Engraftment of transduced cells was assessed using vector gene marking in PBMCs
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | VCN in Peripheral Blood Mononuclear Cells (PBMCs) | 0.600 copies/cell |
| OTL-101* On-Study and CUP Subjects | VCN in Peripheral Blood Mononuclear Cells (PBMCs) | 0.625 copies/cell |
Primary
Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils)
Engraftment of transduced cells was assessed using vector gene marking in granulocytes (neutrophils)
Time frame: 36 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101* On-Study Subjects | Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils) | 0.240 copies/cell |
| OTL-101* On-Study and CUP Subjects | Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils) | 0.280 copies/cell |
Secondary
EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)
Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 90.00 percentage of participants |
| OTL-101* On-Study and CUP Subjects | EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 95.00 percentage of participants |
| HSCT Controls Without MRD | EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 80.00 percentage of participants |
| HSCT Controls With MRD | EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 60.00 percentage of participants |
| All HSCT Controls | EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 66.67 percentage of participants |
p-value: =0.645Log Rank
p-value: =0.299Log Rank
p-value: =0.2Log Rank
p-value: =0.028Log Rank
p-value: =0.259Log Rank
p-value: =0.044Log Rank
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 3-years post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.95% CI: [-32.05, 61.97]
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 3-years post treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.95% CI: [-10.72, 65.87]
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with EvFS at 3-years post-treatment with OTL-101\* (on-study). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study subjects.95% CI: [-15.24, 54.59]
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 3-years post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.95% CI: [-13.7, 63.54]
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 3-years post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.95% CI: [2.29, 68.45]
Comparison: Percentage of patients with EvFS at 3-years post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with EvFS at 3-years post-treatment with OTL-101\* (on-study and CUP). Results are reported as percentage difference in EvFS of historical control group from OTL-101\* on-study and CUP subjects.95% CI: [2.04, 56.36]
Secondary
Infection Rate
The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens.
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | Infection Rate | 0.14 Infection rate per person per year |
| OTL-101* On-Study and CUP Subjects | Infection Rate | 0.14 Infection rate per person per year |
| HSCT Controls Without MRD | Infection Rate | 0.13 Infection rate per person per year |
| HSCT Controls With MRD | Infection Rate | 0.17 Infection rate per person per year |
| All HSCT Controls | Infection Rate | 0.16 Infection rate per person per year |
Secondary
OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)
Overall survival (OS) is defined as the percentage of subjects alive at 36 months post- treatment with OTL-101\* or HSCT
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101* On-Study Subjects | OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 100 percentage of participants |
| OTL-101* On-Study and CUP Subjects | OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 100 percentage of participants |
| HSCT Controls Without MRD | OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 100 percentage of participants |
| HSCT Controls With MRD | OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 88.89 percentage of participants |
| All HSCT Controls | OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years) | 92.86 percentage of participants |
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.95% CI: [-22.41, 48.25]
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study subjects.95% CI: [-28.1, 34.23]
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.95% CI: [-10.01, 48.25]
Comparison: Percentage of patients with OS at 3-years post-treatment in the historical control groups (all historical controls) were compared to the percentage of study patients with OS at 3-years post-treatment with OTL-101\* (on study and CUP). Results are reported as percentage difference in OS of historical control group from OTL-101\* on-study and CUP subjects.95% CI: [-12.91, 33.87]