Acute Myeloid LeukemiaPhase 1/2TRANSATRANCT02717884
Study of Sensitization of Non-M3 AML Blasts to ATRA by Epigenetic Treatment With Tranylcypromine (TCP)
A Phase 1/2 study testing tranylcypromine, all-trans retinoic acid and cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Michael Luebbert at 6 sites in Germany.
Trial summary
The objective of the phase I part of the trial is the determination of the maximum tolerated dose (MTD) of TCP (Tranylcypromine) in combination with fixed-dose ATRA (all-trans-retinoic acid) and with fixed-dose AraC (Cytarabine) and to derive the recommended phase II dose (RP2D) in patients with non-APL AML or MDS for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- tranylcypromine, all-trans retinoic acid and cytarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 6 sitesGermany
- Study dates
- May 2015to Dec 2021
- 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
- Patients eligible for inclusion in this trial must meet all of the following criteria:
- Patients >18 years (no upper age limit);
- AML (WHO) or intermediate or higher risk MDS/ Chronic Myelomonocytic Leukemia (CMML) (IPSS-R >3.0);
- No standard treatment available (comorbidities, higher age, refractoriness to standard or salvage chemotherapy and allografting, azanucleosides failure*);
- Patients with < 30.000 leukocytes/µl;
- Eastern Cooperative Oncology Group (ECOG) 0,1,2;
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- Written informed consent obtained according to international guidelines and local laws;
- Ability to understand the nature of the trial and the trial related procedures and to comply with them.
- Azanucleosides failure is defined as 1) no response after at least three (AML) or six (MDS) cycles of azacitidine or decitabine, 2) disease progression under treatment or 3) grade 3-4 non-hematologic toxicity.
Who cannot join
- Patients eligible for this trial must not meet any of the following criteria:
- Acute promyelocytic leukemia (APL, French-American-British classification system (FAB) M3);
- Eligibility for standard induction or consolidation chemotherapy, immediate allografting, or a hypomethylating agent;
- AML with central nervous system (CNS) involvement;
- AraC treatment within one month prior to registration;
- Prior exposure to histone deacetylase inhibitors, including sodium valproate within one month prior to registration;
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- Stem cell transplant patient with graft-versus-host disease (GvHD) or under systemic immunosuppression;
- Previous gastrointestinal surgery that might interfere with drug absorption;
- Pheochromocytoma;
- Carcinoid tumor;
- Confirmed or suspected cerebrovascular disease;
- Vascular malformations including aneurysm;
- Severe renal insufficiency;
- Severe or poorly controlled hypertension;
- Severe cardiovascular disease;
- Hepatic insufficiency/liver disease;
- Porphyria;
- Diabetes insipidus;
- History or presence of malignant hyperthermia;
- Known psychiatric disorders;
- Known allergy against soy beans or peanuts;
- Known hypersensitivity to or intolerance of one of the trial drugs or its constituents (e.g. lactose, corn starch, indigocarmine (TCP), corn starch (AraC), other retinoids (ATRA));
- Simultaneous intake of the prohibited medication, incl. linezolid, that is likely to cause interactions (see detailed list study protocol);
- Patients who refuse to follow study-specific dietary guidelines;
- Known or persistent abuse of medication, drugs or alcohol;
- Current or planned pregnancy, nursing period;
- Failure to use safe methods of contraception;
- Simultaneous participation in other interventional trials which could interfere with this trial and/or participation before the end of a required restriction period;
- Participation in a clinical trial within the last 30 days before the start of this trial
- Persons who are in a relationship of dependence/employment with the sponsor or the investigator;
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites, 6 recruiting
- Recruiting
Universitätsklinik Düsseldorf, Medical School Duesseldorf
Düsseldorf, 40225
Andrea Kündgen, MD, PD Dr., +49 211 811 ext. 6338, kuendgen@med.uni-duesseldorf.de
Ulrike Spiegelberg, +49 211 811 ext. 7714, spiegelberg@med.uni-duesseldorf.de
- Recruiting
Universitätsklinikum Frankfurt Main, Medical School Frankfurt
Frankfurt am Main, 60590
Tobias Berg, MD, Dr., +49 69 6301 ext. 84004, tobias.berg@kgu.de
Gesine Bug, MD, PD Dr., +49 69 6301 ext. 7369, gesine.bug@kgu.de
- Recruiting
Universitätsklinikum Freiburg, Medical School Freiburg
Freiburg im Breisgau, 79106
Michael Lübbert, MD, Prof., +49 761 270 ext. 35340, michael.luebbert@uniklinik-freiburg.de
Alexandra Schulz, MSc, +49 761 270 ext. 36710, alexandra.schulz@uniklinik-freiburg.de
- Recruiting
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Alwin Krämer, MD, Prof., +49 6221 ext. 5637750, a.kraemer@Dkfz-Heidelberg.de
Anne-Marie Geueke, +49 6221 ext. 568006, anne-marie.geueke@med.uni-heidelberg.de
- Recruiting
Klinikum München rechts der Isar, Medical School Munich rechts der Isar
München, Munich, 81675
Katharina Götze, MD, Prof., +49 89 4140 ext. 5618, katharina.goetze@mri.tum.de
Sandra Eckert, +49 89 4140 ext. 5637, sandra.eckert@mri.tum.de
- Recruiting
Universitätsklinikum Tübingen, Medical School Tuebingen
Tübingen, Tuebingen, 72076
Helmut R Salih, MD, Prof., +49 7071 29 ext. 83275, helmut.salih@med.uni-tuebingen.de
Heinz Schwarz, SN, +49 7071 29 ext. 82883, heinz.schwarz@med.uni-tuebingen.de
About this study
Official title: Phase I/II Study of Sensitization of Non-M3 Acute Myeloid Leukemia (AML) Blasts to All-trans Retinoic Acid (ATRA) by Epigenetic Treatment With Tranylcypromine (TCP), an Inhibitor of the Histone Lysine Demethylase 1 (LSD1)
The objective of the phase I part of the trial is the determination of the maximum tolerated dose (MTD) of TCP (Tranylcypromine) in combination with fixed-dose ATRA (all-trans-retinoic acid) and with fixed-dose AraC (Cytarabine) and to derive the recommended phase II dose (RP2D) in patients with non-APL AML or MDS for whom no standard treatment is available or who failed azanucleoside treatment.
The objective of the phase II part of the trial is a first evaluation of the efficacy of TCP at the RP2D in combination with fixed-dose ATRA and with fixed-dose AraC as basis for further investigations of TCP
Read the detailed description
Study treatment: TCP + ATRA + AraC Four dose levels of TCP (20 mg, 40 mg, 60 mg, 80 mg on days 1-28) will be examined in combination with fixed dose ATRA (45 mg/m2 on days 10-28) and fixed-dose AraC (40 mg on days 1-10) in the first cycle.
In further cycles patients will be treated in the same manner, except for ATRA which will be administered continuously with a nine-day interruption at the beginning of every fourth cycle.
Follow-up per patient: Until twelve months after registration of the last patient.
Duration of intervention per patient: Until relapse/progression, unacceptable toxicity or until twelve months after registration of the last patient, whatever occurs first
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Being tested
- tranylcypromine, all-trans retinoic acid, cytarabine
- Keywords
- AML, MDS, relapsed, trans-retinoic acid ATRA, epigenetic treatment, non-M3 AML blasts, tranylcypromine TCP, LSD1, refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tranylcypromineDrug
Also called TCP, Jatrosom®
TCP p.o., daily either 20, 40, 60, 80** mg/day, (28d/cycle)
**TCP doses will be slowly increased during cycle 1 and slowly decreased at end of treatment (for details see study protocol)
all-trans retinoic acidDrug
Also called ATRA, Vesanoid®
45mg/m2 (days 10-28), CAVE: ATRA will be administered without interruption until inclusively cycle 3. At the beginning of the cycle 4 a nine-day break corresponding to the first nine days of the AraC treatment will be performed, thereafter the ATRA-therapy will be continued with a nine-day interruption every fourth cycle. That means that the therapy in cycles 1, 4, 7, 10, 13 etc. In other cycles ATRA will be given without interruption
cytarabineDrug
Also called Alexan®, AraC
40mg s.c. (days 1-10)
| Study group | Role | What they receive |
|---|---|---|
| TCP, ATRA, Cytarabine | Experimental | Phase I part:
The rolling-six phase I design will be used to determine the MTD of TCP in combination with fixed-dose of ATRA and with fixed-dose AraC in patients with AML/MDS.
Intervention: Four dose levels of TCP (20 mg, 40 mg, 60 mg, 80 mg** on days 1-28) will be examined in combination with ATRA (45 mg/m2 on days 10-28) and with fixed-dose AraC (40 mg on days 1-10) in the first cycle. In case of dose-limiting toxicity (DLT) on the starting level 1 of 20 mg a de-escalation to dose level of 10 mg (level -1) will be investigated.
**TCP dose will be slowly increased to achieve the necessary dose level and slowly tapered off at the end of treatment Receives: Drug: tranylcypromine; Drug: all-trans retinoic acid; Drug: cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD determination of TCP in combination with fixed-dose of ATRA and with fixed-dose Cytarabine;
MTD determination of TCP in combination with fixed-dose of ATRA and with fixed-dose Cytarabine;
Measured: first 28 days of treatment
Secondary outcomes (2)
Objective best response
(CR complete remission, CRi complete remission with incomplete blood count recovery, PR partial remission)
Measured: through study completion, an average of one year
Overall survival (OS)
Overall survival (OS)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study startMay 2015
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michael Luebbert
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Freiburg
- Responsible party
- Sponsor-investigator, Michael Luebbert, University Hospital Freiburg
- Investigators
- Michael Lübbert, MD, Prof., Principal investigator, Medical Center - University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02717884
- Sponsor's protocol ID
- 00806 UKF
- Acronym
- TRANSATRA
- Status last verified
- Oct 2018
- First submitted
- 4 Feb 2016
- Last updated
- 18 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Sensitization of Non-M3 Acute Myeloid Leukemia (AML) Blasts to All-trans Retinoic Acid (ATRA) by Epigenetic Treatment With Tranylcypromine (TCP), an Inhibitor of the Histone Lysine Demethylase 1 (LSD1)
- ClinicalTrials.gov ID
- NCT02717884
- Acronym / sponsor ID
- TRANSATRA / 00806 UKF
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Keywords
- AML, MDS, relapsed, trans-retinoic acid ATRA, epigenetic treatment, non-M3 AML blasts, tranylcypromine TCP, LSD1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Michael LuebbertUniversity, hospital or other
- Collaborators
- University Hospital Freiburg
- Study start
- May 2015
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the phase I part of the trial is the determination of the maximum tolerated dose (MTD) of TCP (Tranylcypromine) in combination with fixed-dose ATRA (all-trans-retinoic acid) and with fixed-dose AraC (Cytarabine) and to derive the recommended phase II dose (RP2D) in patients with non-APL AML or MDS for whom no standard treatment is available or who failed azanucleoside treatment.
The objective of the phase II part of the trial is a first evaluation of the efficacy of TCP at the RP2D in combination with fixed-dose ATRA and with fixed-dose AraC as basis for further investigations of TCP
Detailed description
Study treatment: TCP + ATRA + AraC Four dose levels of TCP (20 mg, 40 mg, 60 mg, 80 mg on days 1-28) will be examined in combination with fixed dose ATRA (45 mg/m2 on days 10-28) and fixed-dose AraC (40 mg on days 1-10) in the first cycle.
In further cycles patients will be treated in the same manner, except for ATRA which will be administered continuously with a nine-day interruption at the beginning of every fourth cycle.
Follow-up per patient: Until twelve months after registration of the last patient.
Duration of intervention per patient: Until relapse/progression, unacceptable toxicity or until twelve months after registration of the last patient, whatever occurs first
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCP, ATRA, Cytarabine | Experimental | Drug: tranylcypromine, Drug: all-trans retinoic acid, Drug: cytarabinePhase I part: The rolling-six phase I design will be used to determine the MTD of TCP in combination with fixed-dose of ATRA and with fixed-dose AraC in patients with AML/MDS. Intervention: Four dose levels of TCP (20 mg, 40 mg, 60 mg, 80 mg** on days 1-28) will be examined in combination with ATRA (45 mg/m2 on days 10-28) and with fixed-dose AraC (40 mg on days 1-10) in the first cycle. In case of dose-limiting toxicity (DLT) on the starting level 1 of 20 mg a de-escalation to dose level of 10 mg (level -1) will be investigated. **TCP dose will be slowly increased to achieve the necessary dose level and slowly tapered off at the end of treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients >18 years (no upper age limit);
- AML (WHO) or intermediate or higher risk MDS/ Chronic Myelomonocytic Leukemia (CMML) (IPSS-R >3.0);
- No standard treatment available (comorbidities, higher age, refractoriness to standard or salvage chemotherapy and allografting, azanucleosides failure*);
- Patients with < 30.000 leukocytes/µl;
- Eastern Cooperative Oncology Group (ECOG) 0,1,2;
Key exclusion criteria (30 listed)
- Acute promyelocytic leukemia (APL, French-American-British classification system (FAB) M3);
- Eligibility for standard induction or consolidation chemotherapy, immediate allografting, or a hypomethylating agent;
- AML with central nervous system (CNS) involvement;
- AraC treatment within one month prior to registration;
- Prior exposure to histone deacetylase inhibitors, including sodium valproate within one month prior to registration;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tranylcypromineAlso: TCP, Jatrosom®TCP p.o., daily either 20, 40, 60, 80** mg/day, (28d/cycle) **TCP doses will be slowly increased during cycle 1 and slowly decreased at end of treatment (for details see study protocol) | Drug | TCP, ATRA, Cytarabine |
| all-trans retinoic acidAlso: ATRA, Vesanoid®45mg/m2 (days 10-28), CAVE: ATRA will be administered without interruption until inclusively cycle 3. At the beginning of the cycle 4 a nine-day break corresponding to the first nine days of the AraC treatment will be performed, thereafter the ATRA-therapy will be continued with a nine-day interruption every fourth cycle. That means that the therapy in cycles 1, 4, 7, 10, 13 etc. In other cycles ATRA will be given without interruption | Drug | TCP, ATRA, Cytarabine |
| cytarabineAlso: Alexan®, AraC40mg s.c. (days 1-10) | Drug | TCP, ATRA, Cytarabine |
Primary outcome
MTD determination of TCP in combination with fixed-dose of ATRA and with fixed-dose Cytarabine;
Time frame: first 28 days of treatment
MTD determination of TCP in combination with fixed-dose of ATRA and with fixed-dose Cytarabine;
2 secondary outcomes
Objective best response
Time frame: through study completion, an average of one year
Overall survival (OS)
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Lübbert, MD, Prof. principal investigator
Medical Center - University of Freiburg
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing tranylcypromine, all-trans retinoic acid and cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Michael Luebbert at 6 sites 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 30 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 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 Michael Lübbert, MD, Prof. (+49 761 270 ext. 35340, michael.luebbert@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD determination of TCP in combination with fixed-dose of ATRA and with fixed-dose Cytarabine; (time frame: first 28 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Oct 2018.