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AMLPhase 1/2TCP-AMLNCT02261779

Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible

A Phase 1/2 study testing Tranylcypromine and Tretinoin in people with AML, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AML
What is being tested?
Tranylcypromine and Tretinoin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteGermany
Study dates
Sep 2014to Sep 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must provide written informed consent prior to performance of study-specific procedures or assessments which are not routinely performed for diagnosis or monitoring of AML, and the subjects must be willing to comply with treatment and to follow up assessments and procedures
  • Histologically or cytologically confirmed diagnosis of AML relapsed after or refractory to at least one induction regimen, or patients with AML at initial diagnosis who are not eligible for allogeneic transplant or intensive induction chemotherapy (investigator´s choice; for example reduced general state), except for AML M3 (acute promyelocytic leukemia).
  • Age > 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 (see Appendix, 3.2)
  • Measurable disease burden (blasts in bonemarrow (BM) and/or peripheral blood (PB), extramedullary blasts [chloroma])
  • Able to swallow and retain oral medication
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  • A life expectancy of at least 4 weeks
  • Adequate contraception methods
  • Adequate organ function

Who cannot join

  • Patients with more than 20.000/µl leukocytes in the peripheral blood that cannot be controlled by Hydroxyurea.
  • Patients with a valid option for intensive chemotherapy and/ or stem cell transplantation. (Patients after allogeneic stem cell transplant must be off immunosuppressive agents for at least 2 weeks prior to study entry and Graft- versus host disease must have resolved to Grade <= 2)
  • Patients with less than 30% blasts in the bone marrow at the time of diagnosis. They should receive Azacytidine monotherapy.
  • History of cancer that according to the Investigator might confound the assessment of the endpoints of the study
  • Uncontrolled peptic ulcer disease or clinically significant gastrointestinal abnormalities which interfere with oral dosing or any unstable or serious concurrent condition (e.g., active uncontrolled infection)
  • Poorly controlled hypertension (defined as systolic blood pressure (SBP) of ≥170 mmHg). Note: Initiation or adjustment of antihypertensive medication is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/ DBP(diastolic blood pressure) values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for he study.
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  • Prolongation of corrected QT interval (QTc) > 480 ms
  • History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction (MI), unstable angina, symptomatic peripheral vascular disease, class 3 or 4 congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • History of cerebrovascular infarction or bleeding, pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti- coagulant agents for at least 6 weeks are eligible
  • Evidence of serious active bleeding or bleeding diathesis (except for bleeding or petechiae due to AML- related thrombocytopenia which will be treated using platelet transfusions). Also, patients with known endobronchial lesions and/ or lesions infiltrating major pulmonary vessels will be excluded from the study due to excess risk of bleeding.
  • Prior major surgery or trauma within 28 days prior to first dose of study drug
  • Treatment with an investigational agent within 21 days or 5 half-life, whichever is longer prior to the first dose of study drug.
  • Concurrent cytoreductive chemotherapy except hydroxyurea.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to Tretinoin, Retinoids, soya, peanuts or Tranylcypromine.
  • Patients with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
  • Patients with known epilepsy or patients with known psychiatric affections (bipolar disorder, schizophrenia, suicidal patients)
  • Pregnant or lactating and actively breastfeeding patients
  • Patients who are indignant to comply with nutritional conditions (see Protocol)
  • Poorly adjusted diabetes mellitus
  • Patients with hereditary Galactose-Intolerance, Lactase-Intolerance or Glucose-Galactose-Malabsorption
  • Known drug or alcohol abuse
  • Phaeochromocytoma or carcinoid tumor
  • Known cerebral vascular disease or other malformation of vessels (e.g. aneurysma)
  • Diabetes insipidus
  • Patients taking any of the following prohibited medication due to interaction with a) tretinoin and b) TCP.

Trial locations and contacts

1 site in 1 country.

Carsten Mueller-Tidow, Prof. contact

+493455572924

carsten.mueller-tidow@uk-halle.de

Petra Tschanter, Dr. contact

+493455577288

petra.tschanter@uk-halle.de

Germany1 site, 1 recruiting

  • Universitaetsklinikum Halle

    Halle, D-06120

    Contact Person

    Recruiting

Other trials in Germany

About this study

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

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.

Conditions
AML
Being tested
Tranylcypromine, Tretinoin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TranylcypromineDrug

    Also called Jatrosom

  • TretinoinDrug

    Also called Vesanoid

Study groups in NCT02261779
Study groupRoleWhat they receive
Tretinoin & TranylcypromineExperimentalTretinoin 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
Receives: Drug: Tranylcypromine; Drug: Tretinoin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Analysis of the cumulative response rate (CR,CRp, CRi, PR)

    Disease status will be assessed by bone marrow analyses

    Measured: every 28 day cycle

Secondary outcomes (3)

  1. number of participants with adverse events as a measure of safety and tolerability

    Measured: one year

  2. overall survival

    Measured: 2 years

  3. treatment effects of promotor genes

    To assess the cumulative incidence and degree of histone methylation of promotor genes in AML blasts after treatment with Tretinoin and tranylcpromine

    Measured: 2 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2014 (estimated)
  2. Study startSep 2014
  3. Primary completionSep 2017 (estimated)
  4. Study completionSep 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02261779
Sponsor's protocol ID
UKM_04_12_TCP_ATRA_AML
Other IDs
2012-002154-23
Acronym
TCP-AML
Status last verified
Jul 2015
First submitted
23 Sep 2014
Last updated
7 Jul 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tranylcypromine and Tretinoin in people with AML, run by Martin-Luther-Universität Halle-Wittenberg at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Carsten Mueller-Tidow, Prof. (+493455572924, carsten.mueller-tidow@uk-halle.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Analysis of the cumulative response rate (CR,CRp, CRi, PR) (time frame: every 28 day cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02261779.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2015; AzTrials last refreshed its copy on 8 Nov 2026.

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