INFUSION OF BPX-501 (DONOR T CELLS TRANSDUCED WITH THE IC9 SUICIDE GENE) AFTER ?/? T-CELL DEPLETED HAPLO-HSCT IN CHILDREN WITH ACUTE LEUKEMIA: PRELIMINARY RESULTS OF A PHASE I-II TRIAL.
(Abstract release date: 05/19/16)
EHA Library. Bertaina A. 06/11/16; 135279; S523
Dr. Alice Bertaina
Contributions
Contributions
Abstract
Abstract: S523
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Room H5
Background
We recently conducted a prospective study (NCT01810120) which showed that haploHSCT after depletion of α/β T cells is a suitable and effective option for those children in need of an allograft and lacking an immediately available HLA-identical donor. However, recovery of adaptive T-cell immunity remains suboptimal and some patients experienced either relapse of the original disease or severe viral infections.
Aims
In light of these considerations, strategies aimed at accelerating early recovery of adaptive T-cell immunity are desirable.
Methods
We designed a phase I/II trial aimed at testing the safety and efficacy of post-transplant infusion of donor-derived T cells transduced with the new iC9 suicide gene (BPX-501) in children with either malignant or non-malignant disorders (NCT02065869); enrollment started in December 2014. Cells are administered within 14+4 days after haploHSCT. The phase I portion of the trial consisted of a classical 3+3 design with 3 cohorts, receiving escalating doses of BPX-501 cells of 2.5x105, 5x105, and 1x106 cells/kg, respectively. Patients included in the phase II portion received the highest tolerated/recommended dose identified during the phase I portion of the study. As of February 15th 2016, 13 children with acute leukemia either in first or second complete remission (CR1/CR2) have been transplanted; 7 were males and 6 were females. Median age at HSCT was 6.5 years (range 0.9-16.1); 10 pts had acute lymphoblastic leukemia (ALL) and 3 acute myeloid leukemia (AML). All pts transplanted in CR1 had either poor cytogenetic/molecular characteristics or high levels of minimal residual disease (MRD) at the end of induction therapy. All children received >10x106 CD34+ cells/Kg and <1x105 αβ+ T cells/Kg. A myeloablative regimen was given to all children, who also received as prophylaxis of graft-versus-host disease (GVHD) anti-thymocyte globulin (12 mg/kg over 3 days, from -5 to -3). Rituximab (200 mg/m2) was administered on day -1 to further prevent EBV-related lymphoproliferative disorders. No pharmacological GvHD prophylaxis was employed after HSCT.
Results
Sustained primary engraftment occurred in all pts. The median time to infusion of BPX-501 cells was 16 days (range 13-18) after HSCT; median cell viability was 91% (range 65-97). Only one child developed gut and liver acute GVHD requiring infusion of AP1903, which controlled the disease. Five pts experienced skin-only grade I-II acute GVHD, this leading to a cumulative incidence (CI) of 38%. None of the patients at risk developed chronic GVHD. No patient died for transplant-related complications. One pt relapsed at 4 month after HSCT, the CI of disease recurrence being 12%. With a median follow-up of 6 months (range 3-12), the Kaplan Meier estimate of leukemia-free survival (LFS) is 88% (95% CI 38.7-98.1) compared to 76.6% (95% CI 65.4-84.5) in the 77 CR1/CR2 ALL/AML patients included in our previous study. BPX-501 cells progressively expanded over time after the infusion and are persisting, contributing to the recovery of adaptive T-cell immunity.
Conclusion
These data indicate that the infusion of BPX-501 cells in children with acute leukemia given selectively manipulated haploHSCT results in the absence of transplantation-related mortality and chronic GVHD. Although the median observation time is still limited, the CI of disease recurrence is promising.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute leukemia, Gene therapy, Pediatric, Transplant
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Room H5
Background
We recently conducted a prospective study (NCT01810120) which showed that haploHSCT after depletion of α/β T cells is a suitable and effective option for those children in need of an allograft and lacking an immediately available HLA-identical donor. However, recovery of adaptive T-cell immunity remains suboptimal and some patients experienced either relapse of the original disease or severe viral infections.
Aims
In light of these considerations, strategies aimed at accelerating early recovery of adaptive T-cell immunity are desirable.
Methods
We designed a phase I/II trial aimed at testing the safety and efficacy of post-transplant infusion of donor-derived T cells transduced with the new iC9 suicide gene (BPX-501) in children with either malignant or non-malignant disorders (NCT02065869); enrollment started in December 2014. Cells are administered within 14+4 days after haploHSCT. The phase I portion of the trial consisted of a classical 3+3 design with 3 cohorts, receiving escalating doses of BPX-501 cells of 2.5x105, 5x105, and 1x106 cells/kg, respectively. Patients included in the phase II portion received the highest tolerated/recommended dose identified during the phase I portion of the study. As of February 15th 2016, 13 children with acute leukemia either in first or second complete remission (CR1/CR2) have been transplanted; 7 were males and 6 were females. Median age at HSCT was 6.5 years (range 0.9-16.1); 10 pts had acute lymphoblastic leukemia (ALL) and 3 acute myeloid leukemia (AML). All pts transplanted in CR1 had either poor cytogenetic/molecular characteristics or high levels of minimal residual disease (MRD) at the end of induction therapy. All children received >10x106 CD34+ cells/Kg and <1x105 αβ+ T cells/Kg. A myeloablative regimen was given to all children, who also received as prophylaxis of graft-versus-host disease (GVHD) anti-thymocyte globulin (12 mg/kg over 3 days, from -5 to -3). Rituximab (200 mg/m2) was administered on day -1 to further prevent EBV-related lymphoproliferative disorders. No pharmacological GvHD prophylaxis was employed after HSCT.
Results
Sustained primary engraftment occurred in all pts. The median time to infusion of BPX-501 cells was 16 days (range 13-18) after HSCT; median cell viability was 91% (range 65-97). Only one child developed gut and liver acute GVHD requiring infusion of AP1903, which controlled the disease. Five pts experienced skin-only grade I-II acute GVHD, this leading to a cumulative incidence (CI) of 38%. None of the patients at risk developed chronic GVHD. No patient died for transplant-related complications. One pt relapsed at 4 month after HSCT, the CI of disease recurrence being 12%. With a median follow-up of 6 months (range 3-12), the Kaplan Meier estimate of leukemia-free survival (LFS) is 88% (95% CI 38.7-98.1) compared to 76.6% (95% CI 65.4-84.5) in the 77 CR1/CR2 ALL/AML patients included in our previous study. BPX-501 cells progressively expanded over time after the infusion and are persisting, contributing to the recovery of adaptive T-cell immunity.
Conclusion
These data indicate that the infusion of BPX-501 cells in children with acute leukemia given selectively manipulated haploHSCT results in the absence of transplantation-related mortality and chronic GVHD. Although the median observation time is still limited, the CI of disease recurrence is promising.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute leukemia, Gene therapy, Pediatric, Transplant
Abstract: S523
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Room H5
Background
We recently conducted a prospective study (NCT01810120) which showed that haploHSCT after depletion of α/β T cells is a suitable and effective option for those children in need of an allograft and lacking an immediately available HLA-identical donor. However, recovery of adaptive T-cell immunity remains suboptimal and some patients experienced either relapse of the original disease or severe viral infections.
Aims
In light of these considerations, strategies aimed at accelerating early recovery of adaptive T-cell immunity are desirable.
Methods
We designed a phase I/II trial aimed at testing the safety and efficacy of post-transplant infusion of donor-derived T cells transduced with the new iC9 suicide gene (BPX-501) in children with either malignant or non-malignant disorders (NCT02065869); enrollment started in December 2014. Cells are administered within 14+4 days after haploHSCT. The phase I portion of the trial consisted of a classical 3+3 design with 3 cohorts, receiving escalating doses of BPX-501 cells of 2.5x105, 5x105, and 1x106 cells/kg, respectively. Patients included in the phase II portion received the highest tolerated/recommended dose identified during the phase I portion of the study. As of February 15th 2016, 13 children with acute leukemia either in first or second complete remission (CR1/CR2) have been transplanted; 7 were males and 6 were females. Median age at HSCT was 6.5 years (range 0.9-16.1); 10 pts had acute lymphoblastic leukemia (ALL) and 3 acute myeloid leukemia (AML). All pts transplanted in CR1 had either poor cytogenetic/molecular characteristics or high levels of minimal residual disease (MRD) at the end of induction therapy. All children received >10x106 CD34+ cells/Kg and <1x105 αβ+ T cells/Kg. A myeloablative regimen was given to all children, who also received as prophylaxis of graft-versus-host disease (GVHD) anti-thymocyte globulin (12 mg/kg over 3 days, from -5 to -3). Rituximab (200 mg/m2) was administered on day -1 to further prevent EBV-related lymphoproliferative disorders. No pharmacological GvHD prophylaxis was employed after HSCT.
Results
Sustained primary engraftment occurred in all pts. The median time to infusion of BPX-501 cells was 16 days (range 13-18) after HSCT; median cell viability was 91% (range 65-97). Only one child developed gut and liver acute GVHD requiring infusion of AP1903, which controlled the disease. Five pts experienced skin-only grade I-II acute GVHD, this leading to a cumulative incidence (CI) of 38%. None of the patients at risk developed chronic GVHD. No patient died for transplant-related complications. One pt relapsed at 4 month after HSCT, the CI of disease recurrence being 12%. With a median follow-up of 6 months (range 3-12), the Kaplan Meier estimate of leukemia-free survival (LFS) is 88% (95% CI 38.7-98.1) compared to 76.6% (95% CI 65.4-84.5) in the 77 CR1/CR2 ALL/AML patients included in our previous study. BPX-501 cells progressively expanded over time after the infusion and are persisting, contributing to the recovery of adaptive T-cell immunity.
Conclusion
These data indicate that the infusion of BPX-501 cells in children with acute leukemia given selectively manipulated haploHSCT results in the absence of transplantation-related mortality and chronic GVHD. Although the median observation time is still limited, the CI of disease recurrence is promising.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute leukemia, Gene therapy, Pediatric, Transplant
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Room H5
Background
We recently conducted a prospective study (NCT01810120) which showed that haploHSCT after depletion of α/β T cells is a suitable and effective option for those children in need of an allograft and lacking an immediately available HLA-identical donor. However, recovery of adaptive T-cell immunity remains suboptimal and some patients experienced either relapse of the original disease or severe viral infections.
Aims
In light of these considerations, strategies aimed at accelerating early recovery of adaptive T-cell immunity are desirable.
Methods
We designed a phase I/II trial aimed at testing the safety and efficacy of post-transplant infusion of donor-derived T cells transduced with the new iC9 suicide gene (BPX-501) in children with either malignant or non-malignant disorders (NCT02065869); enrollment started in December 2014. Cells are administered within 14+4 days after haploHSCT. The phase I portion of the trial consisted of a classical 3+3 design with 3 cohorts, receiving escalating doses of BPX-501 cells of 2.5x105, 5x105, and 1x106 cells/kg, respectively. Patients included in the phase II portion received the highest tolerated/recommended dose identified during the phase I portion of the study. As of February 15th 2016, 13 children with acute leukemia either in first or second complete remission (CR1/CR2) have been transplanted; 7 were males and 6 were females. Median age at HSCT was 6.5 years (range 0.9-16.1); 10 pts had acute lymphoblastic leukemia (ALL) and 3 acute myeloid leukemia (AML). All pts transplanted in CR1 had either poor cytogenetic/molecular characteristics or high levels of minimal residual disease (MRD) at the end of induction therapy. All children received >10x106 CD34+ cells/Kg and <1x105 αβ+ T cells/Kg. A myeloablative regimen was given to all children, who also received as prophylaxis of graft-versus-host disease (GVHD) anti-thymocyte globulin (12 mg/kg over 3 days, from -5 to -3). Rituximab (200 mg/m2) was administered on day -1 to further prevent EBV-related lymphoproliferative disorders. No pharmacological GvHD prophylaxis was employed after HSCT.
Results
Sustained primary engraftment occurred in all pts. The median time to infusion of BPX-501 cells was 16 days (range 13-18) after HSCT; median cell viability was 91% (range 65-97). Only one child developed gut and liver acute GVHD requiring infusion of AP1903, which controlled the disease. Five pts experienced skin-only grade I-II acute GVHD, this leading to a cumulative incidence (CI) of 38%. None of the patients at risk developed chronic GVHD. No patient died for transplant-related complications. One pt relapsed at 4 month after HSCT, the CI of disease recurrence being 12%. With a median follow-up of 6 months (range 3-12), the Kaplan Meier estimate of leukemia-free survival (LFS) is 88% (95% CI 38.7-98.1) compared to 76.6% (95% CI 65.4-84.5) in the 77 CR1/CR2 ALL/AML patients included in our previous study. BPX-501 cells progressively expanded over time after the infusion and are persisting, contributing to the recovery of adaptive T-cell immunity.
Conclusion
These data indicate that the infusion of BPX-501 cells in children with acute leukemia given selectively manipulated haploHSCT results in the absence of transplantation-related mortality and chronic GVHD. Although the median observation time is still limited, the CI of disease recurrence is promising.
Session topic: Stem cell transplantation - Clinical 1
Keyword(s): Acute leukemia, Gene therapy, Pediatric, Transplant
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