Contributions
Abstract: EP748
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Although many patients with acute myeloid leukemia (AML) achieve morphological complete remission (CR) due to improved treatment modalities, the majority of them still relapse leading to poor long-term prognosis. These relapses are due to residual leukemic stem cells that can be identified as minimal/measurable residual disease (MRD), with MRD serving as a predictive factor for relapse and mortality. Elimination of MRD in patients having reached CR is seen as essential for optimal and persistent clinical responses.
Aims
A promising approach is the development of adoptive immunotherapies aimed at directly eradicating residual tumor cells using natural killer (NK) cells. NK cells can be applied clinically in an allogeneic setting, enabling the supply of high numbers of immune effector cells, which were not exposed to cytotoxic chemotherapeutics. A proprietary ex vivo expansion and differentiation method in a fully closed, automated manufacturing platform was developed to generate GTA002, an “off-the-shelf” (allogeneic), cryopreserved NK cell preparation, generated from CD34+ hematopoietic stem and progenitor cells derived from umbilical cord blood. The safety and tolerability of the product was demonstrated in a Phase I trial in elderly patients with AML (Dolstra et al. 2017).
Methods
We are currently conducting a prospective 2-stage, open-label, single arm, multicenter Phase I/IIa trial to evaluate the safety and efficacy of GTA002 in 33 adults with AML who are in CR with MRD and who are not proceeding to allogeneic HSCT (ClinicalTrials.gov NCT04632316). After providing informed consent, patients enrolled in the clinical trial receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine followed by up to 3 NK cell infusions 4 days apart and will be followed up for 12 months. The dose escalation stage will assess the safety and tolerability of repeat NK cell infusions in a 3+3 design with 3 cohorts and a cumulative dose range of 325 to 3,000 x106 viable NK cells. The expansion stage will evaluate the safety, tolerability and efficacy of NK cell infusions in 24 additional subjects.
Results
Enrollment in the first cohort (one single NK cell infusion) started in December 2020. Preliminary safety data from the first cohort will be discussed at the meeting.
Conclusion
The overall objective of the trial is to evaluate whether GTA002 is safe and if it can eradicate MRD, thereby reducing the relapse risk and mortality in subjects with AML who are in CR with MRD and who do not proceed to allogeneic HSCT.
Keyword(s): Acute myeloid leukemia, Adoptive immunotherapy, NK cell
Abstract: EP748
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Although many patients with acute myeloid leukemia (AML) achieve morphological complete remission (CR) due to improved treatment modalities, the majority of them still relapse leading to poor long-term prognosis. These relapses are due to residual leukemic stem cells that can be identified as minimal/measurable residual disease (MRD), with MRD serving as a predictive factor for relapse and mortality. Elimination of MRD in patients having reached CR is seen as essential for optimal and persistent clinical responses.
Aims
A promising approach is the development of adoptive immunotherapies aimed at directly eradicating residual tumor cells using natural killer (NK) cells. NK cells can be applied clinically in an allogeneic setting, enabling the supply of high numbers of immune effector cells, which were not exposed to cytotoxic chemotherapeutics. A proprietary ex vivo expansion and differentiation method in a fully closed, automated manufacturing platform was developed to generate GTA002, an “off-the-shelf” (allogeneic), cryopreserved NK cell preparation, generated from CD34+ hematopoietic stem and progenitor cells derived from umbilical cord blood. The safety and tolerability of the product was demonstrated in a Phase I trial in elderly patients with AML (Dolstra et al. 2017).
Methods
We are currently conducting a prospective 2-stage, open-label, single arm, multicenter Phase I/IIa trial to evaluate the safety and efficacy of GTA002 in 33 adults with AML who are in CR with MRD and who are not proceeding to allogeneic HSCT (ClinicalTrials.gov NCT04632316). After providing informed consent, patients enrolled in the clinical trial receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine followed by up to 3 NK cell infusions 4 days apart and will be followed up for 12 months. The dose escalation stage will assess the safety and tolerability of repeat NK cell infusions in a 3+3 design with 3 cohorts and a cumulative dose range of 325 to 3,000 x106 viable NK cells. The expansion stage will evaluate the safety, tolerability and efficacy of NK cell infusions in 24 additional subjects.
Results
Enrollment in the first cohort (one single NK cell infusion) started in December 2020. Preliminary safety data from the first cohort will be discussed at the meeting.
Conclusion
The overall objective of the trial is to evaluate whether GTA002 is safe and if it can eradicate MRD, thereby reducing the relapse risk and mortality in subjects with AML who are in CR with MRD and who do not proceed to allogeneic HSCT.
Keyword(s): Acute myeloid leukemia, Adoptive immunotherapy, NK cell