Ignite Creation Date:
2025-12-25 @ 3:55 AM
Ignite Modification Date:
2026-03-03 @ 7:40 PM
Study NCT ID:
NCT02273102
Status:
COMPLETED
Last Update Posted:
2020-07-21
First Post:
2014-10-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of TCP-ATRA for Adult Patients With AML and MDS
Sponsor:
University of Miami
Organization:
Study Overview
Official Title:
A Phase 1 Dose Escalation Study of Tranylcypromine (TCP) in Combination With ATRA (Tretinoin) for Adult Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)
Status:
COMPLETED
Status Verified Date:
2020-07
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:
TCP-ATRA
Brief Summary:
Acute Myeloid Leukemia (AML) is a diverse disease that is fatal in the majority of patients. Acute promyelocytic leukemia (APL) however, a subtype of AML accounting for 5% of all cases, is very curable. APL cells are highly sensitive to the retinoid all-trans-retinoic acid (ATRA), which effectively differentiates the leukemic clone. Over 80% of APL patients can be cured with ATRA based therapies. For patients with non-APL AML, ATRA has little effect. Consequently, 85% of these patients will succumb to their disease despite conventional approaches. Little is known about mechanisms of resistance to ATRA in non-APL AML. This knowledge gap limits the use of ATRA in a disease that already has few effective therapies. The investigators' preliminary data suggest that non-APL AML cells can be re-sensitized to ATRA when combined with lysine-specific demethylase 1 (LSD 1) inhibitors. The investigators' publication in Nature Medicine showed that LSD1 inhibition with tranylcypromine (TCP), unlocked the ATRA-driven therapeutic response in non-APL AML. Notably, treatment with ATRA and TCP markedly diminished the engraftment of primary human AML cells in murine models, indicating that the combination may target leukemia-initiating cells (LIC). The investigators' data identify LSD1 as a therapeutic target and strongly suggest that it may contribute to ATRA resistance in non-APL AML. The investigators' central hypothesis is that ATRA combined with TCP will be safe and effective in a clinical population, and that this approach will suppress LICs and restore myeloid differentiation programs in patients with non-APL AML. Testing this hypothesis with the phase I clinical trial outlined in this protocol, will establish a new treatment paradigm in AML and extend the important anti-cancer effects of ATRA to all AML subtypes.
Detailed Description:
None
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: