Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00329498
Status:
SUSPENDED
Last Update Posted:
2006-10-26
First Post:
2006-05-22
Brief Title:
L-Ascorbic Acid Depletion to Treat Acute Myeloid Leukemia and Myelodysplastic Syndromes
Sponsor:
Samsung Medical Center
Organization:
Samsung Medical Center
Study Overview
Official Title:
Manipulation of L-Ascorbic Acid Level For The Treatment of Selected Cases Of Acute Myeloid Leukemia and Myelodysplastic Syndromes
Status:
SUSPENDED
Status Verified Date:
2006-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To document therapeutic gain achieved by cyclic application of L-ascorbic acid LAA supplementation and depletion while confirming safety and avoidance of clinically significant scurvy in chemorefractory patients with acute myeloid leukemia AML and myelodysplastic syndromes MDS
Detailed Description:
The seminal discovery that the in vitro growth of malignant cells could be absolutely dependent on L-ascorbic acid LAA was originally published in Sciene The cell culture assay used with a mouse plasmacytoma model in this discovery was based on colony formation and was essentially the same as the one used to grow normal hemopoietic colonies such as CFU-GM and CFU-G from normal bone marrow specimens Subsequent analysis of the growth factors for these CFUs using this same culture system eventually led to the discovery of colony stimulating factors such as GM-CSF and G-CSF now widely used clinically Human leukemia specifically acute myeloid leukemia AML cell colonies also grow well in this culture system as shown by extensive cell biology studies In addition cells from patients with myelodysplastic syndrome MDS a significant proportion of them progressing to AML behave similarly to AML cells in this culture system In particular both AML and MDS are identical in that the growth of colonies is enhanced by addition of LAA to the cell culture media in a high proportion of these patients
The large volume of in vitro data thus generated including correlations with direct clinical relevance is increasingly convincing that lowering of LAA levels could potentially be developed and utilized as a treatment for specific hemopoeitic malignancies This was particularly attractive in view of the fact that the growth of normal hemopoietic colonies such as CFU-GM and CFU-G is never enhanced by LAA Such an absolute selectivity would predict a lack of clinical adverse hemopoetic events from an intervention which lowered LAA levels We also had seemingly-contradictory data that the growth of colonies from AML and MDS patients could be suppressed by addition of LAA infrequently but sometimes profoundly However detailed dose response analysis later clarified this low physiologic doses enhance and high pharmacologic doses suppress formation of leukemic colonies From a therapeutic perspective we would have greater expectations for a depletion strategy than for supplementation because 1 leukemic suppression by addition of LAA is often accompanied by some mild suppression of the normal CFU and therefore is not absolutely selective and 2 LAA supplementation has been clinically tested in a variety of solid tumors with controversial outcomes
Therefore our original protocol was developed primarily to accomplish lowering of LAA levels with a subsequent oral LAA supplementation used primarily to prevent scurvy and only secondarily for possible benefit However with the first patient there was a strong indication of antileukemic effects during both the LAA depletion and supplementation phases Based on this encouragement the protocol was amended to formally alternate depletion with supplementation and to utilize intravenous IV administration of LAA to achieve high dose supplementation With 17 subsequent subjects having been treated this study of the safety and efficacy of cyclic manipulation of LAA levels has demonstrated beneficial outcome in a high proportion of refractory and terminal patients with AML or MDS Moreover growing laboratory evidence being produced provides a molecular basis for these clinical outcomes
The large volume of in vitro data thus generated including correlations with direct clinical relevance is increasingly convincing that lowering of LAA levels could potentially be developed and utilized as a treatment for specific hemopoeitic malignancies This was particularly attractive in view of the fact that the growth of normal hemopoietic colonies such as CFU-GM and CFU-G is never enhanced by LAA Such an absolute selectivity would predict a lack of clinical adverse hemopoetic events from an intervention which lowered LAA levels We also had seemingly-contradictory data that the growth of colonies from AML and MDS patients could be suppressed by addition of LAA infrequently but sometimes profoundly However detailed dose response analysis later clarified this low physiologic doses enhance and high pharmacologic doses suppress formation of leukemic colonies From a therapeutic perspective we would have greater expectations for a depletion strategy than for supplementation because 1 leukemic suppression by addition of LAA is often accompanied by some mild suppression of the normal CFU and therefore is not absolutely selective and 2 LAA supplementation has been clinically tested in a variety of solid tumors with controversial outcomes
Therefore our original protocol was developed primarily to accomplish lowering of LAA levels with a subsequent oral LAA supplementation used primarily to prevent scurvy and only secondarily for possible benefit However with the first patient there was a strong indication of antileukemic effects during both the LAA depletion and supplementation phases Based on this encouragement the protocol was amended to formally alternate depletion with supplementation and to utilize intravenous IV administration of LAA to achieve high dose supplementation With 17 subsequent subjects having been treated this study of the safety and efficacy of cyclic manipulation of LAA levels has demonstrated beneficial outcome in a high proportion of refractory and terminal patients with AML or MDS Moreover growing laboratory evidence being produced provides a molecular basis for these clinical outcomes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None