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AzTrials

Acute Myeloid LeukemiaPhase 2AML-ViVANCT02942758

Low-dose AZA, Pioglitazone, ATRA Versus Standard-dose AZA in Patients >=60 Years With Refractory AML

A Phase 2 study testing low-dose Azacitidine, Pioglitazone and ATRA in people with Acute Myeloid Leukemia, run by University Hospital Regensburg at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Diagnosis: Acute myeloid leukemia refractory to intensive induction chemotherapy; Age ≥ 60 years, no upper age limit; Study drug: low-dose azacitidine, pioglitazone, ATRA; Safety Run-In Phase; randomized Phase II, open-label Safety Run-In Phase: Based on a 3 + 3 modified design, the tolerable dose of ATRA for the… Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
low-dose Azacitidine, Pioglitazone and ATRA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteGermany
Study dates
10 Apr 2017to 25 Mar 2020
Phase
Phase 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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with confirmed diagnosis of acute myeloid leukemia (AML) who are refractory* to induction therapy and not eligible for further intensive induction therapy based on documented medical reasons (e.g. disease characteristics or patient characteristics), or
  • Patients with confirmed diagnosis of acute myeloid leukemia (AML) who are refractory* to induction therapy and not immediate candidates for allogeneic HSCT (bridge to transplant is allowed)
  • refractory to induction therapy is defined as no CR, no CRi and no PR (according to standard criteria, see Section 11.2.3) after at least one intensive induction therapy including at least 5 days of cytarabine 100-200 mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 500 mg/m² per cycle and at least 2 days of an anthracycline (e.g. daunorubicin, idarubicin).
  • Age ≥ 60; no upper age limit
  • ECOG performance status of ≤ 2 at screening
  • To control hyperleukocytosis or extramedullary involvement, medication with hydroxyurea is allowed up to 24h before start of study treatment. In case of hyperleukocytosis hydroxyurea should be given and start of study treatment should be delayed until leukocyte counts are < 20 x 10^9/L.
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  • Female subjects of childbearing potential* may participate, providing they meet the following conditions:
  • Have a negative pregnancy test (serum or urine with a sensitivity of at least 25 mIU/mL; local laboratory) within 72 hours prior to starting study therapy. They must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence** from heterosexual contact.
  • Agree to practice true abstinence** from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with two effective methods of contraception (e.g., oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) without interruption during the study therapy (including dose interruptions), and for 3 months after discontinuation of study drugs.
  • A female subject of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
  • True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Male patients with a female partner of childbearing potential must agree to abstain from sexual intercourse or to the use of at least two effective contraceptive methods (e.g., synthetic condoms with spermicide, etc) at screening and throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last study treatment.
  • Signed written informed consent.

Who cannot join

  • Known or suspected hypersensitivity to the study drugs and/or any excipients
  • Patients with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); PML-RARA, or with variant translocations
  • Acute myeloid leukemia (AML) with isocitratdehydrogenase (IDH) 1 or 2 mutations if results are available from the central AMLSG reference laboratories
  • ECOG performance status > 2
  • Inadequate cardiac, hepatic and/or renal function at Screening Visit defined as:
  • heart failure NYHA II-IV
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  • unstable angina pectoris
  • total bilirubin, ALT, AST > 2.5 x upper normal serum level
  • Creatinine > 1.5 x upper normal serum level
  • Active central nervous system involvement
  • Uncontrolled infection
  • Uncontrolled diabetes mellitus
  • Patients with a "currently active" second malignancy requiring active therapy other than non-melanoma skin cancers (except for hormonal/antihormonal treatment, e.g. in prostate or breast cancer)
  • Patients with "currently active" bladder cancer or bladder cancer in their history, patients with risk factors for bladder cancer (e.g. exposure to aromatic amines or heavy tobacco smoker), or macrohematuria of unknown origin
  • Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
  • Known or suspected active alcohol or drug abuse
  • Known positive for HIV, active HBV or HCV infection
  • No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation.
  • Treatment with any other clinical study drug within 14 days before the first administration of the investigational drugs or at any time during the study
  • Breast feeding woman or women with a positive pregnancy test at Screening Visit
  • Male patients with a female partner of childbearing potential not willing to abstain from sexual intercourse or to the use of at least two effective contraceptive methods (e.g., synthetic condoms with spermicide, etc) at screening and throughout the course of the study and for 3 months following the last study treatment.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital Regensburg

    Regensburg, 93053

Other trials in Germany

About this study

Official title: Randomized Phase II Trial With Safety run-in Phase Evaluating Low-dose AZA, ATRA and Pioglitazone Versus Standard Dose Azacitidine in Patients >=60 Years With AML Who Are Refractory to Standard Induction Chemotherapy

Diagnosis: Acute myeloid leukemia refractory to intensive induction chemotherapy; Age ≥ 60 years, no upper age limit; Study drug: low-dose azacitidine, pioglitazone, ATRA; Safety Run-In Phase; randomized Phase II, open-label

  • Safety Run-In Phase: Based on a 3 + 3 modified design, the tolerable dose of ATRA for the randomized phase II is defined.
  • Phase II: Experimental Arm: low-dose azacitidine, pioglitazone, ATRA; Standard Arm: standard-dose azacitidine; in both arms patients can receive further cycles (with no limit to the number given) as long as clinically appropriate
Being tested
low-dose Azacitidine, Pioglitazone, ATRA, standard-dose AZA
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • low-dose AzacitidineDrug

    Also called Vidaza

    Azacitidine 75 mg/d s.c. for 7 days, repeated 28-day treatment cycle

  • PioglitazoneDrug

    Also called Actos

    Pioglitazone 45 mg p.o. continuously from day 1

  • ATRADrug

    Also called All-trans-retinoic acid; Vesanoid

    ATRA *45 mg/m² p.o. from day 1 to 28, 15 mg/m² from day 29 continuously; *this regimen will be chosen for the first dose to be evaluated.

  • standard-dose AZADrug

    Also called Vidaza

    Azacitidine 75 mg/m²/d s.c. for 7 days, repeated 28-day treatment cycle

Study groups in NCT02942758
Study groupRoleWhat they receive
low-dose AZA / ATRA / PioglitazoneExperimentallow-dose azacitidine (75 mg/d), ATRA, pioglitazone
Receives: Drug: low-dose Azacitidine; Drug: Pioglitazone; Drug: ATRA
standard-dose AZAActive comparatorstandard-dose azacitidine (75mg/m²/d)
Receives: Drug: standard-dose AZA

What is being measured

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

  1. overall Survival

    Measured: 3 years

Secondary outcomes (10)

  1. complete remission (CR) rate

    Measured: 3 years

  2. complete remission with incomplete blood count recovery (CRi) rate

    Measured: 3 years

  3. partial remission (PR) rate

    Measured: 3 years

  4. hematological improvement (HI) rate

    Measured: 3 years

  5. cumulative incidence of relapse (CIR)

    Measured: 3 years

  6. cumulative incidence of death (CID)

    Measured: 3 years

  7. cumulative incidence of relapse event free survival (EFS)

    Measured: 3 years

  8. event free survival (EFS)

    Measured: 3 years

  9. Quality of Life (QLQ-C30)

    Measured: 3 years

  10. Incidence and intensity of adverse events (AEs)

    Measured: 3 years

Timeline

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

  1. First posted24 Oct 2016 (estimated)
  2. Study start10 Apr 2017
  3. Primary completion25 Mar 2020
  4. Study completion25 Mar 2020

Why it stopped: Due to financial reasons.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02942758
Sponsor's protocol ID
AMLSG26-16
Acronym
AML-ViVA
Status last verified
May 2024
First submitted
18 Oct 2016
Last updated
8 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Klobuch S, Steinberg T, Bruni E, Mirbeth C, Heilmeier B, Ghibelli L, Herr W, Reichle A, Thomas S. Biomodulatory Treatment With Azacitidine, All-trans Retinoic Acid and Pioglitazone Induces Differentiation of Primary AML Blasts Into Neutrophil Like Cells Capable of ROS Production and Phagocytosis. Front Pharmacol. 2018 Nov 27;9:1380. doi: 10.3389/fphar.2018.01380. eCollection 2018.

    PubMed 30542286

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing low-dose Azacitidine, Pioglitazone and ATRA in people with Acute Myeloid Leukemia, run by University Hospital Regensburg 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 13 inclusion and 21 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: stopped early, as of the sponsor's last update on 8 May 2024. 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 phase mean?

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?

The study was stopped early (reason given: Due to financial reasons.). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

overall Survival (time frame: 3 years). 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 NCT02942758, which also lists 1 linked publication.

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 8 May 2024.

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