STUDY TITLE
A Randomized, Phase 2, Two-Arm, Open-Label, Multicenter, Study of Folotyn® (Pralatrexate Injection) with and without Oral Leucovorin to Prevent or Reduce Mucositis in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL)
BACKGROUND
1.a Defining Peripheral T-Cell Lymphomas (PTCL)
Peripheral or mature T-cell lymphomas are subset of aggressive non-Hodgkin lymphomas (NHL) that comprise approximately 10-15% of all newly diagnosed cases of NHL in the United State. According to the 2008 World Health Organization (WHO) Classification schema, there are 18 subtypes of mature T- and natural killer (NK) cell neoplasms (Swerdlow 2008). Various subtypes of T- and NK-cell lymphomas are known to express the cell surface marker CD30; most notably, sACLC, in which CD30 expression is a hallmark of the diagnosis (Savage 2008). These difficult-to-treat lymphomas are often grouped together for enrollment in clinical trials based on their universal dismal outcomes. Five-year …show more content…
This mechanism of action results in a potential for broad spectrum cytotoxic activity against tumor cells and rapidly dividing nucleated cells. The improved antitumor effects of Pralatrexate are likely due to the more effective internalization by the 1-carbon reduced folate carrier (RFC-1), and the subsequent accumulation in tumor cells through the formation of polyglutamylated metabolites. 75,77 RFC-1 is a fetal oncoprotein that is predominantly expressed on fetal and malignant tissue, and is felt to be the principal means through which Pralatrexate, though not necessarily other anti-folates, enters the cell. This carrier protein has evolved to efficiently transport reduced natural folates into highly proliferative cells, in order to meet he demands for purine and pyrimidine nucleotides during deoxyribonucleic acid (DNA)
A Randomized, Phase 2, Two-Arm, Open-Label, Multicenter, Study of Folotyn® (Pralatrexate Injection) with and without Oral Leucovorin to Prevent or Reduce Mucositis in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL)
BACKGROUND
1.a Defining Peripheral T-Cell Lymphomas (PTCL)
Peripheral or mature T-cell lymphomas are subset of aggressive non-Hodgkin lymphomas (NHL) that comprise approximately 10-15% of all newly diagnosed cases of NHL in the United State. According to the 2008 World Health Organization (WHO) Classification schema, there are 18 subtypes of mature T- and natural killer (NK) cell neoplasms (Swerdlow 2008). Various subtypes of T- and NK-cell lymphomas are known to express the cell surface marker CD30; most notably, sACLC, in which CD30 expression is a hallmark of the diagnosis (Savage 2008). These difficult-to-treat lymphomas are often grouped together for enrollment in clinical trials based on their universal dismal outcomes. Five-year …show more content…
This mechanism of action results in a potential for broad spectrum cytotoxic activity against tumor cells and rapidly dividing nucleated cells. The improved antitumor effects of Pralatrexate are likely due to the more effective internalization by the 1-carbon reduced folate carrier (RFC-1), and the subsequent accumulation in tumor cells through the formation of polyglutamylated metabolites. 75,77 RFC-1 is a fetal oncoprotein that is predominantly expressed on fetal and malignant tissue, and is felt to be the principal means through which Pralatrexate, though not necessarily other anti-folates, enters the cell. This carrier protein has evolved to efficiently transport reduced natural folates into highly proliferative cells, in order to meet he demands for purine and pyrimidine nucleotides during deoxyribonucleic acid (DNA)