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Acute Myeloid LeukemiaPhase 1NCT03516760

Dose-escalating Phase I Trial With GEM333 in Patients With Acute Myeloid Leukemia

A Phase 1 study testing GEM333 in people with Acute Myeloid Leukemia and Relapsed AML, run by AvenCell Europe GmbH at 7 sites 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

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM333 in patients with acute myeloid leukemia (AML). This AML was relapsed after previous therapy or was refractory to the standard therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GEM333
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
7 sitesGermany
Study dates
11 Apr 2018to 14 Jun 2022
Phase
Phase 1
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

  • Male or female patients, ≥ 18 years of age
  • Documented definitive diagnosis of CD33 positive AML (according to standard of care testing) in
  • 2a. Patients having received standard induction chemotherapy: either refractory to standard induction treatment, or is relapsed within 6 months after achieving 1st CR, or relapsed later than 6 months after 1st CR and refractory to standard salvage regimen, or relapse after ≥ 2nd CR and not eligible for curative treatment (i.e. allogeneic stem cell transplantation)
  • 2b. Patients not eligible for standard induction chemotherapy: either refractory or progressive after at least 1 cycle of demethylating agents
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Life expectancy of at least 2 months
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  • Adequate renal and hepatic laboratory assessments:
  • Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 45% as assessed by transthoracal two-dimensional echocardiography
  • A female of childbearing potential may be enrolled providing she has a negative pregnancy test at screening visit and is routinely using a highly effective method of birth control (pearl index of ≤ 1 required) resulting in a low failure rate (e.g. hormonal contraception, intrauterine device, total sexual abstinence or sterilization) until 3 months from the last study drug administration. Male patients must also practice a highly effective method of birth control.
  • Able to give written informed consent
  • Weight ≥ 45 kg

Who cannot join

  • Acute promyelocytic leukemia (t15;17)
  • Manifestation of AML in central nervous system
  • Leukocytosis > 10 Gpt/L
  • Cardiac disease: i.e. heart failure NYHA III or IV; unstable coronary artery disease (Myocardial Infarction more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Patients undergoing renal dialysis
  • Pulmonary disease with clinical relevant hypoxia (need for continuous oxygen inhalation)
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  • Active central nervous diseases (e.g. parkinson, multiple sclerosis, epilepsy) and stroke within last 6 months
  • Active infectious disease considered by investigator to be incompatible with protocol
  • Allogeneic stem cell transplantation within last three months or GvHD requiring immune-suppressive therapy
  • Major surgery within 28 days prior to start of study medication
  • Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
  • Checkpoint inhibitors und CD33 targeting agents within 8 weeks prior to start of trial medication
  • Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
  • Treatment with any investigational drug substance or experimental therapy within 4 weeks prior to start of trial medication or 5 half lives of the substance prior to start of trial medication
  • Pregnant or breastfeeding women
  • Psychologic disorders, drug and/or significant active alcohol abuse
  • Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  • Known hypersensitivity to GEM333 excipients
  • Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
  • Incapability of understanding purpose and possible consequences of the trial
  • Patients who should not be included according to the opinion of the investigator

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Charité Universitätsmedizin

    Berlin, 13353

  • Universitätsklinikum Dresden

    Dresden, Saxony, 01307

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, Hesse, 60590

  • Universitätsmedizin Mannheim

    Mannheim, Baden-Wurttemberg, 68167

  • Universitätsklinikum Marburg

    Marburg, Hesse, 35039

  • Klinikum rechts der Isar

    München, Bavaria, 81675

  • Universitätsklinikum Würzburg

    Würzburg, Bavaria, 97080

Other trials in Germany

About this study

Official title: A Multicenter, Open-label, Dose-escalating, Phase I Trial With GEM333, a CD33 Targeted Bispecific Antibody Engaging T-cells, in Relapsed or Refractory Acute Myeloid Leukemia

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM333 in patients with acute myeloid leukemia (AML). This AML was relapsed after previous therapy or was refractory to the standard therapy.

Being tested
GEM333
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.

  • GEM333Drug

    infusion of GEM333; administered intravenously and continuously over 10 days

Study groups in NCT03516760
Study groupRoleWhat they receive
GEM333Experimentalapplication of GEM333, a CD33 targeted bispecific antibody engaging T-cells
Receives: Drug: GEM333

What is being measured

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

  1. Maximum tolerated dose (MTD)

    MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.

    Measured: End of Treatment (EOT) +8 days resp. +28 days (DLT period)

  2. Incidence of dose limiting toxicity (DLT)

    Dose Limiting Toxicity is defined as any event at least possibly related to IMP (complete definition provided protocol)

    Measured: End of Treatment (EOT) +8 days resp. +28 days

  3. Incidence and intensity of adverse events graded according to CTCAE V4.03

    Measured: End of Treatment (EOT) +8 days resp. +28 days

Secondary outcomes (10)

  1. Recommended phase 2 dose

    The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.

    Measured: From start of treatment until up to +28 days after last treatment cycle (1 initial cycle + max. 2 additional cycles per patient). Each cycle consists of 10 days treatment plus DLT evaluation period (8 resp. 28 days, depending on blast clearance).

  2. Complete remission (CR)

    bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L

    Measured: until two years after start of study medication

  3. Composite complete remission (CRc) rate

    Rate at any time point, defined as the proportion of patients having either CR or CRi

    Measured: until two years after start of study medication

  4. Partial Remission (PR)

    All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.

    Measured: until two years after start of study medication

  5. Disease stabilization (DS)

    Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR

    Measured: until two years after start of study medication

  6. Best response rate

    Defined as the best observed response at any time point during observational period.

    Measured: until two years after start of study medication

  7. Duration of CRc

    Defined as the number of days between the date of CR/CRi achievement and the date of the last assessment confirming CR/CRi

    Measured: until two years after start of study medication

  8. Duration of PR

    Defined as the number of days between the date of PR achievement and the date of the last assessment confirming PR.

    Measured: until two years after start of study medication

  9. Progression free survival (PFS)

    Is defined as the time from first treatment with GEM333 until disease progression or death from any cause

    Measured: until two years after start of study medication

  10. Overall survival

    Defined as the number of days between the first study drug administration and death from any cause

    Measured: until two years after start of study medication

Timeline

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

  1. First posted4 May 2018
  2. Study start11 Apr 2018
  3. Primary completion14 Jun 2022
  4. Study completion14 Jun 2022

Why it stopped: The actions and measures to be taken to restart the trial could not be implemented which made the premature termination inevitability.

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03516760
Sponsor's protocol ID
GEM333-01
Other IDs
2017-001707-77, 2017
Status last verified
Sep 2022
First submitted
6 Apr 2018
Last updated
29 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GEM333 in people with Acute Myeloid Leukemia and Relapsed AML, run by AvenCell Europe GmbH at 7 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 11 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 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 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.

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: The actions and measures to be taken to restart the trial could not be implemented which made the premature termination inevitability.). 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?

Maximum tolerated dose (MTD) (time frame: End of Treatment (EOT) +8 days resp. +28 days (DLT period)). The study lists 3 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 NCT03516760.

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 29 Sep 2022.

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