Acute Lymphoblastic Leukemia, Anemia, Aplastic, Anemia, Sickle Cell, Cytopenia, Diamond Blackfan Anemia, Fanconi Anemia, Hemoglobinopathies, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes, Primary Immunodeficiency, Thalassemia
Conditions
Keywords
Long term follow up, Gene-modified cells, ALL, AML, hematologic neoplasms, hematologic malignancies, anemia, congenital cytopenia, primary immune deficiencies, hemoglobinopathy
Brief summary
This is a long-term follow up study evaluating the safety of BPX-501 T cells (rivogenlecleucel) and infused in pediatric patients previously enrolled on the BP-004 study.
Detailed description
Subjects enrolled on the BP-004 study who have completed or discontinued from the study, and are beyond Day 180 will be requested to enroll on this long-term follow up protocol. Long term follow up for gene therapy clinical and safety endpoints will continue up to 15 years.
Interventions
DRUGRimiducid
Rimiducid is administered to treat chronic graft versus host disease
BIOLOGICALrivogenlecleucel
donor T-cells modified with iCasp safety switch
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent by the patient or the patient's guardian for children who are minors * Enrolled on BP-004 protocol, received BPX-501 infusion, completed or discontinued from the study, and are beyond Day +180.
Exclusion criteria
* Lack of parents'/guardian's informed consent for children who are minors * Loss of allograft prior to 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 1 and 2 years after rivogenlecleucel infusion | Overall survival (OS) in both malignant and non-malignant subpopulations at 1 and 2 years in the Intent-to-Treat (ITT) Population |
| Incidence of Disease-free Survival | 1 and 2 years after rivogenlecleucel infusion | KM Parameter Estimates of disease-free survival (DFS) in the non-malignant subpopulation at 1 and 2 years in the Intent-to-Treat (ITT) Population |
| Relapse-free Survival | 1 and 2 years after rivogenlecleucel infusion | Kaplan-Meier Parameter Estimates of Relapse-free survival rate (number of patients survived without experiencing a recurrence) at the 1-year and 2-year timepoints in the Intent-to-Treat (ITT) Population in the malignant study arm (patients with a malignant reason for their transplant). ITT Population: Includes all patients treated with HSCT who received rivogenlecleucel at the dose of 1×10E6 cells/kg |
Countries
Italy
Participant flow
Recruitment details
Study BP-404 was the long-term follow-up for patients enrolled in the BP-004 study at the Italian site as well as patients in Saudi Arabia (patients enrolled and treated in the UK who moved back after hematopoietic stem cell transplantation. The below participant flow information pertains to all patients in the BP-004 study (NCT02065869)
Pre-assignment details
3 Enrolled patients did not undergo hematopoietic stem cell transplantation (HSCT)
Participants by arm
| Arm | Count |
|---|---|
| Rimiducid and Rivogenlecleucel Rimiducid: to treat uncontrolled GVHD in patients who have received rivogenlecleucel Rimiducid will be given at 0.4 mg/kg weight (intravenous infusion)
No further rivogenlecleucel infusions are planned. Patients who received rivogenlecleucel in the BP-004 study will be evaluated for long-term safety and efficacy. | 184 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 7 |
| Overall Study | Disease relapse | 16 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | No rivogenlecleucel cells infused (non-evaluable) | 7 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rimiducid and Rivogenlecleucel |
|---|---|
| Age, Continuous | 5.8 years |
| Age, Customized 12 to ≤ 18 years | 35 Participants |
| Age, Customized 18 to ≤ 26 years | 1 Participants |
| Age, Customized 2 to < 12 years | 105 Participants |
| Age, Customized < 2 years | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 162 Participants |
| Sex: Female, Male Female | 83 Participants |
| Sex: Female, Male Male | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 171 | 0 / 16 |
| other Total, other adverse events | 140 / 171 | 9 / 16 |
| serious Total, serious adverse events | 52 / 171 | 7 / 16 |
Outcome results
Primary
Incidence of Disease-free Survival
KM Parameter Estimates of disease-free survival (DFS) in the non-malignant subpopulation at 1 and 2 years in the Intent-to-Treat (ITT) Population
Time frame: 1 and 2 years after rivogenlecleucel infusion
Population: ITT Population: Includes all patients treated with HSCT who received rivogenlecleucel at the dose of 1×10E6 cells/kg~Study BP-404 is the long-term follow-up study of patients of the BP-004 study who were enrolled at the Italian and Saudi Arabia sites. There is a second long-term follow-up study (BP-004 UK) for patients enrolled at the UK sites. The below results include data from both the BP-404 study and the BP-004 UK study. Individual results for either study are not available.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Malignant | Incidence of Disease-free Survival | 1 Year | Event occurred | 4 Participants |
| Malignant | Incidence of Disease-free Survival | 1 Year | Censored | 7 Participants |
| Malignant | Incidence of Disease-free Survival | 1 Year | At Risk [defined as: Total participants - (Event occurred + Censored)] | 69 Participants |
| Malignant | Incidence of Disease-free Survival | 2 Years | Event occurred | 5 Participants |
| Malignant | Incidence of Disease-free Survival | 2 Years | Censored | 12 Participants |
| Malignant | Incidence of Disease-free Survival | 2 Years | At Risk [defined as: Total participants - (Event occurred + Censored)] | 63 Participants |
Primary
Overall Survival
Overall survival (OS) in both malignant and non-malignant subpopulations at 1 and 2 years in the Intent-to-Treat (ITT) Population
Time frame: 1 and 2 years after rivogenlecleucel infusion
Population: ITT Population: Includes all patients treated with HSCT who received rivogenlecleucel at the dose of 1×10E6 cells/kg~Study BP-404 is the long-term follow-up study of patients of the BP-004 study who were enrolled at the Italian and Saudi Arabia sites. There is a second long-term follow-up study (BP-004 UK) for patients enrolled at the UK sites. The below results include data from both the BP-404 study and the BP-004 UK study. Individual results for either study are not available.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Malignant | Overall Survival | 1 Year | Censored | 3 Participants |
| Malignant | Overall Survival | 2 Years | Event Occurred | 8 Participants |
| Malignant | Overall Survival | 2 Years | Censored | 4 Participants |
| Malignant | Overall Survival | 1 Year | Event Occurred | 8 Participants |
| Malignant | Overall Survival | 2 Years | At Risk [Defined as: Total participants - (Event Occurred + Censored)] | 50 Participants |
| Malignant | Overall Survival | 1 Year | At Risk [Defined as: Total participants - (Event Occurred + Censored)] | 51 Participants |
| Non-malignant | Overall Survival | 2 Years | At Risk [Defined as: Total participants - (Event Occurred + Censored)] | 63 Participants |
| Non-malignant | Overall Survival | 1 Year | Event Occurred | 3 Participants |
| Non-malignant | Overall Survival | 1 Year | Censored | 8 Participants |
| Non-malignant | Overall Survival | 1 Year | At Risk [Defined as: Total participants - (Event Occurred + Censored)] | 69 Participants |
| Non-malignant | Overall Survival | 2 Years | Censored | 13 Participants |
| Non-malignant | Overall Survival | 2 Years | Event Occurred | 4 Participants |
Primary
Relapse-free Survival
Kaplan-Meier Parameter Estimates of Relapse-free survival rate (number of patients survived without experiencing a recurrence) at the 1-year and 2-year timepoints in the Intent-to-Treat (ITT) Population in the malignant study arm (patients with a malignant reason for their transplant). ITT Population: Includes all patients treated with HSCT who received rivogenlecleucel at the dose of 1×10E6 cells/kg
Time frame: 1 and 2 years after rivogenlecleucel infusion
Population: ITT Population: Includes all patients treated with HSCT who received rivogenlecleucel at the dose of 1×10E6 cells/kg~Study BP-404 is the long-term follow-up study of patients of the BP-004 study who were enrolled at the Italian and Saudi Arabia sites. There is a second long-term follow-up study (BP-004 UK) for patients enrolled at the UK sites. The below results include data from both the BP-404 study and the BP-004 UK study. Individual results for either study are not available.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Malignant | Relapse-free Survival | 1 Year | Event Occurred | 12 Participants |
| Malignant | Relapse-free Survival | 1 Year | Censored | 0 Participants |
| Malignant | Relapse-free Survival | 1 Year | At Risk | 50 Participants |
| Malignant | Relapse-free Survival | 2 Years | Event Occurred | 13 Participants |
| Malignant | Relapse-free Survival | 2 Years | Censored | 1 Participants |
| Malignant | Relapse-free Survival | 2 Years | At Risk | 48 Participants |