Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible (TCP-AML)
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|ClinicalTrials.gov Identifier: NCT02261779|
Recruitment Status : Unknown
Verified July 2015 by Dr. Petra Tschanter, Martin-Luther-Universität Halle-Wittenberg.
Recruitment status was: Recruiting
First Posted : October 10, 2014
Last Update Posted : July 7, 2015
Longterm disease-free survival (DFS) of older patients with acute myeloid leukemia (AML) remains poor. The vast majority of AML patients relapses within two years after start of therapy1,2. In Acute Promyelocytic Leukemia (APL, AML M3), all-trans-retinoic-acid (ATRA; Tretinoin) induces differentiation and subsequently clinical remission. So far effective differentiation therapy does not exist in other AML subtypes. Recent preclinical data suggest that the combinatorial use of ATRA and tranylcypromine (TCP), an irreversible Monoamine-Oxidase (MAO) and Lysin-specific demethylase (LSD) inhibitor that also inhibits LSD1 (a histone H3 Lysine 4 demethylase), induces leukemia cell differentiation and leukemic stem cell exhaustion in vitro and in vivo in non-APL AML subtypes.
In this Phase I/II study the investigators will explore the feasibility, safety, as well as efficacy and of Tretinoin/TCP treatment in patients with relapsed or refractory AML or in patients with AML who are not eligible for intensive treatment. Patients will be treated with daily increasing doses of TCP (initially 10 mg/day, then +10 mg each day up to 80mg/d). After 7 days, ATRA will be added at a fixed dose (45 mg/sqm/day). Overall, 16 evaluable patients are going to be treated. The primary endpoint is the fraction of patients that achieve CR, CRp( complete response with incomplete recovery of platelets), CRi (complete response with incomplete recovery of granulocytes) and PR. Secondary endpoints are tolerability, safety as well as progression-free survival and overall survival. Serum levels of TCP will be regularly analyzed. Pharmacodynamic analyses will be performed with analyses of the inhibition of LSD1 by TCP. Further analyses will address the changes in Histone H3 lysine 4 tri demethylase (H3K4me3) levels in AML blasts and the differentiation status of AML blasts.
Taken together, this Phase I/II study will analyze feasibility, pharmacodynamics and effectivity of ATRA and TCP as differentiation therapy in AML.
|Condition or disease||Intervention/treatment||Phase|
|AML||Drug: Tranylcypromine Drug: Tretinoin||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Pilot Trial of ATRA (Tretinoin) and TCP (Tranylcypromine) in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) and no Intensive Treatment is Possible|
|Study Start Date :||September 2014|
|Estimated Primary Completion Date :||September 2017|
|Estimated Study Completion Date :||September 2017|
Experimental: Tretinoin & Tranylcypromine
Tretinoin started with 45mg/m2 on day 7 for one year, administered orally as soft capsules, Tranylcypromine started with 10mg/d up to a maximum dose of 60mg/d for on year, administered orally as tablets
Other Name: Jatrosom
Other Name: Vesanoid
- Analysis of the cumulative response rate (CR,CRp, CRi, PR) [ Time Frame: every 28 day cycle ]Disease status will be assessed by bone marrow analyses
- number of participants with adverse events as a measure of safety and tolerability [ Time Frame: one year ]
- overall survival [ Time Frame: 2 years ]
- treatment effects of promotor genes [ Time Frame: 2 Years ]To assess the cumulative incidence and degree of histone methylation of promotor genes in AML blasts after treatment with Tretinoin and tranylcpromine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02261779
|Contact: Carsten Mueller-Tidow, Prof.||+firstname.lastname@example.org|
|Contact: Petra Tschanter, Dr.||+email@example.com|
|Halle, Germany, D-06120|
|Contact: Contact Person|
|Principal Investigator:||Carsten Mueller-Tidow, Prof.||Martin-Luther-Universität Halle-Wittenberg|