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Relapsed Adult AMLPhase 1/2RELAXNCT04330820

Trial for Relapsed or Refractory AML Patients Combining Cytarabine and Mitoxantrone With Venetoclax (RELAX)

A Phase 1/2 study testing Venetoclax Oral Tablet in people with Relapsed Adult AML and Refractory AML, run by Technische Universität Dresden at 12 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label Phase I dose-escalation study of oral venetoclax in combination with increasing cytarabine doses plus mitoxantrone to define the safety profile and MTD of cytarabine in subjects with a histologically or cytologically confirmed acute myeloid leukemia who are refractory or suffered a relapse. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Relapsed Adult AML, Refractory AML
What is being tested?
Venetoclax Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
12 sitesGermany
Study dates
6 Apr 2020to 24 Sep 2025
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained before screening.
  • AML according to WHO-2016 criteria, excluding acute promyelocytic leukemia
  • Relapsed from first or second CR after 1-2 cycles of standard induction chemotherapy (which must have included cytarabine with an anthracycline or anthracenedione), including relapse after allogeneic stem cell transplantation (dose escalation and expansion part)
  • Age 18-75 years
  • Fit for intensive chemotherapy, defined by
  • ECOG 0-2, life expectancy > 3months
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  • Adequate hepatic function: ALAT/ASAT/Bilirubin ≤2.5 x ULN*
  • unless considered due to leukemic organ involvement Note: Subjects with Gilbert's Syndrome may have a bilirubin > 2.5 × ULN per discussion between the investigator and Coordinating investigator.
  • Adequate renal function assessed by serum creatinine ≤ 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min
  • Patient is afebrile and hemodynamically stable for at least 72 hours at the time of study medication initiation.
  • Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 30 days after the last dose of study drug.
  • Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
  • Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml)
  • Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days before the first dose of study drug.
  • Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device - IUD) from time point of signing the informed consent until 30 days after the last dose of study drug.
  • Note: At present, it is not known whether the effectiveness of hormonal contraceptives is reduced by venetoclax. For this reason, women should use a barrier method in addition to hormonal contraceptive methods.
  • Sexual abstinence
  • Vasectomy of the sexual partner
  • Inclusion criteria applying for expansion phase (Phase II) only:
  • Primary refractory after 1-2 cycles of standard induction chemotherapy (100 to 200 mg/m2 cytarabine over 7-10 days plus anthracycline or mitoxantrone over 3 days or equivalent treatment, e.g. CPX351) or relapsed from first or second CR after 1-2 cycles of standard induction chemotherapy (which must have included cytarabine with an anthracycline or anthracenedione), including relapse after allogeneic stem cell transplantation
  • Note: Primary refractory disease is defined by either ≥ 20% myeloid blasts on early response assessment around day 15 after start of the most recent induction, or by ≥ 5% myeloid blasts after blood recovery after start of the most recent induction, respectively.

Who cannot join

  • Acute promyelocytic leukemia (AML M3)
  • CNS involvement or subjects with extramedullary disease only
  • Known hypersensitivity to excipients of the preparation or any agent given in association with this study including cytarabine or mitoxantrone
  • Intended hematopoietic stem cell transplantation planned as early conditioning from aplasia without previous blood count recovery
  • Cumulative previous exposure to anthracyclines of >410 mg/m2 doxorubicin equivalents
  • Acute GVHD ≥ grade 2, extensive chronic GVHD or requiring systemic immunosuppressive therapy within 2 weeks prior to start of study treatment
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  • HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections).
  • Inability to swallow oral medications
  • Any malabsorption condition
  • Cardiovascular disability status of New York Heart Association (NYHA) Class ≥ 2.
  • Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
  • Chronic respiratory disease that requires continuous oxygen use.
  • White blood cell count > 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
  • AML relapse treatment with any investigational or commercial drug within 14 days before enrolment. Hydroxyurea is allowed until enrolment to control peripheral WBC counts. Toxic effects of previous investigational drug treatment have to recover to Grade <2.
  • Substance abuse, medical, psychological, or social conditions that may interfere with the subject's cooperation with the requirements of the trial or evaluation of the study results
  • Acute non-hematologic toxicities from any prior anti-leukemia therapy or from previous investigational drugs that have not resolved to Grade <2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Evens (CTCAE), Version 5.0
  • Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment.
  • History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (Occult or prior hepatitis B virus (HBV) infection (defined as negative hepatitis B surface antigen and positive total hepatitis B core antibody) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior but cured hepatitis B are eligible. Patients positive for hepatitis C virus antibody are eligible provided PCR is negative for HCV RNA.)
  • History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C).
  • Live-virus vaccines given within 28 days prior to the initiation of study treatment

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Germany12 sites

  • Klinikum Augsburg, Medizinische Klinik II

    Augsburg, 86156

  • Klinikum Chemnitz, Krankenhaus Küchwald, Klinik für Innere Medizin III

    Chemnitz, 09113

  • Universitätsklinikum Dresden, Medizinische Klinik I

    Dresden, 01307

  • Universitätsklinikum Essen; Zentrum für Innere Medizin

    Essen, 45122

  • Universitätsklinikum Frankfurt am Main, Medizinische Klinik II

    Frankfurt am Main, 60590

  • Universitätsklinikum Schleswig-Holstein Campus Kiel, Klinik für Innere Medizin II

    Kiel, 24105

  • Universitätsklinikum Marburg

    Marburg, 35033

  • Rotkreuzklinikum München, III. Medizinische Abteilung-Hämatologie und Onkologie

    München, 80634

  • Universitätsklinikum Münster, Medizinische Klinik A

    Münster, 48149

  • Klinikum Nürnberg Nord, Klinik für Innere Medizin 5

    Nuremberg, 90419

  • Robert-Bosch-Krankenhaus Hämatologie, Onkologie und Palliativmedizin

    Stuttgart, 70376

  • Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken

    Würzburg, 97080

Other trials in Germany

About this study

Official title: Phase-I/II Trial for Relapsed or Refractory AML Patients Combining Cytarabine and Mitoxantrone With Venetoclax (RELAX)

This is an open-label Phase I dose-escalation study of oral venetoclax in combination with increasing cytarabine doses plus mitoxantrone to define the safety profile and MTD of cytarabine in subjects with a histologically or cytologically confirmed acute myeloid leukemia who are refractory or suffered a relapse. This study will be conducted at multiple centers in Germany.

Read the detailed description
  • To determine safety, tolerability, maximum tolerated dose, and recommended phase II dose of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone in subjects with a relapsed or refractory AML considered fit for intensive salvage therapy.
  • To assess the preliminary efficacy of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone in subjects with a relapsed or refractory AML considered fit for intensive salvage therapy.
Being tested
Venetoclax Oral Tablet
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.

  • Venetoclax Oral TabletDrug

    Also called Cytarabin

    This study will investigate the combination of a fixed maximum venetoclax dose with increasing cytarabine doses plus mitoxantrone in a fixed dose in phase I. In Phase II cytarabine will be given at MDT or RP2D that assessed in phase I.

    The venetoclax dose of 400 mg will be reached by a ramp up over 3 days. Parallel chemotherapy with cytarabine and mitoxantrone will start on day 3.

Study groups in NCT04330820
Study groupRoleWhat they receive
Venetoclax+Cytarabin+ MitoxantronExperimentalThe treatment plan combines a fixed dose of venetoclax and mitoxantrone with increasing doses of cytarabine (V-MAC).
Receives: Drug: Venetoclax Oral Tablet

What is being measured

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

  1. Maximum tolerated dose (= recommended phase II dose) of cytarabine in combination with venetoclax plus mitoxantrone

    number of dose limiting toxicities related to venetoclax per cohort

    Measured: appr. 9 months

  2. CR/CRi rate

    preliminary efficacy of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone

    Measured: appr. 12 months

Secondary outcomes (7)

  1. remission

    Duration of Remission and Depth of remission (MRD)

    Measured: appr. 48 months

  2. Relapse

    Cumulative incidence of relapse

    Measured: appr. 48 months

  3. Relapse-free survival

    number of participants alive without relapse

    Measured: appr. 48 months

  4. Mortality

    Early mortality (within 14 and 30 days)

    Measured: appr. 48 months

  5. Proportion of allogeneic stem cell transplantation

    number of allogeneic stem cell transplantation following response

    Measured: appr. 48 months

  6. incidence and severity of adverse Events [safety and tolerability]

    number and grade of Adverse Events assessed by CTCAE v5.0

    Measured: appr. 48 months

  7. Overall survival

    number of patients alive

    Measured: appr. 48 months

Timeline

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

  1. First posted2 Apr 2020
  2. Study start6 Apr 2020
  3. Primary completion11 Oct 2023
  4. Study completion24 Sep 2025

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
Sequential
Model description
The phase I part will be conducted according to the enhanced algorithms of a 3+3H design (Ji et al. J Clin Oncol 2013). The phase II part will be performed as single stage study adopting the A'Hern design (A'Hern Stat Med 2001).
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04330820
Sponsor's protocol ID
TUD-RELAX1-070
Acronym
RELAX
Status last verified
Aug 2026
First submitted
19 Mar 2020
Last updated
2 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ruhnke L, Schliemann C, Mikesch JH, Stelljes M, Fransecky L, Steffen B, Kaufmann M, Burchert A, Rank A, Hanoun M, Hollein A, Kraus S, Schafer-Eckart K, Hanel M, Haake A, Fiebig F, Kramer M, Zukunft S, Kunadt D, Middeke JM, Sockel K, Schetelig J, Platzbecker U, von Bonin M, Rohnert MA, Oelschlagel U, Wagenfuhr L, Thiede C, Herold S, Poitz D, Stolzel F, Baldus CD, Serve H, Wermke M, Bornhauser M, Rollig C. Venetoclax plus high-dose cytarabine and mitoxantrone as salvage treatment for relapsed or refractory acute myeloid leukaemia (RELAX): a multicentre, single-arm, phase 1/2 trial. Lancet Haematol. 2026 Mar;13(3):e157-e168. doi: 10.1016/S2352-3026(25)00358-8.

    PubMed 41791831

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Venetoclax Oral Tablet in people with Relapsed Adult AML and Refractory AML, run by Technische Universität Dresden at 12 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 22 inclusion and 20 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: finished, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose (= recommended phase II dose) of cytarabine in combination with venetoclax plus mitoxantrone (time frame: appr. 9 months). The study lists 2 primary outcomes in all. 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 NCT04330820, 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 2 Sep 2026.

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