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

September 28, 2022 updated by: AvenCell Europe GmbH

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Charité Universitätsmedizin
    • Baden-Württemberg
      • Mannheim, Baden-Württemberg, Germany, 68167
        • Universitätsmedizin Mannheim
    • Bayern
      • München, Bayern, Germany, 81675
        • Klinikum rechts der Isar
      • Würzburg, Bayern, Germany, 97080
        • Universitätsklinikum Würzburg
    • Hessen
      • Frankfurt am Main, Hessen, Germany, 60590
        • Universitätsklinikum Frankfurt
      • Marburg, Hessen, Germany, 35039
        • Universitätsklinikum Marburg
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitätsklinikum Dresden

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients, ≥ 18 years of age

  2. 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
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  4. Life expectancy of at least 2 months
  5. Adequate renal and hepatic laboratory assessments:
  6. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 45% as assessed by transthoracal two-dimensional echocardiography
  7. 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.
  8. Able to give written informed consent
  9. Weight ≥ 45 kg

Exclusion Criteria:

  1. Acute promyelocytic leukemia (t15;17)
  2. Manifestation of AML in central nervous system
  3. Leukocytosis > 10 Gpt/L
  4. 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
  5. Patients undergoing renal dialysis
  6. Pulmonary disease with clinical relevant hypoxia (need for continuous oxygen inhalation)
  7. Active central nervous diseases (e.g. parkinson, multiple sclerosis, epilepsy) and stroke within last 6 months
  8. Active infectious disease considered by investigator to be incompatible with protocol
  9. Allogeneic stem cell transplantation within last three months or GvHD requiring immune-suppressive therapy
  10. Major surgery within 28 days prior to start of study medication
  11. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
  12. Checkpoint inhibitors und CD33 targeting agents within 8 weeks prior to start of trial medication
  13. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
  14. 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
  15. Pregnant or breastfeeding women
  16. Psychologic disorders, drug and/or significant active alcohol abuse
  17. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  18. Known hypersensitivity to GEM333 excipients
  19. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
  20. Incapability of understanding purpose and possible consequences of the trial
  21. Patients who should not be included according to the opinion of the investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GEM333
application of GEM333, a CD33 targeted bispecific antibody engaging T-cells
Drug: GEM333
infusion of GEM333; administered intravenously and continuously over 10 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: End of Treatment (EOT) +8 days resp. +28 days (DLT period)
MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.
End of Treatment (EOT) +8 days resp. +28 days (DLT period)
Incidence of dose limiting toxicity (DLT)
Time Frame: End of Treatment (EOT) +8 days resp. +28 days
Dose Limiting Toxicity is defined as any event at least possibly related to IMP (complete definition provided protocol)
End of Treatment (EOT) +8 days resp. +28 days
Incidence and intensity of adverse events graded according to CTCAE V4.03
Time Frame: End of Treatment (EOT) +8 days resp. +28 days
End of Treatment (EOT) +8 days resp. +28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Recommended phase 2 dose
Time Frame: 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).
The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
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).
Complete remission (CR)
Time Frame: until two years after start of study medication
bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L
until two years after start of study medication
Composite complete remission (CRc) rate
Time Frame: until two years after start of study medication
Rate at any time point, defined as the proportion of patients having either CR or CRi
until two years after start of study medication
Partial Remission (PR)
Time Frame: until two years after start of study medication
All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.
until two years after start of study medication
Disease stabilization (DS)
Time Frame: until two years after start of study medication
Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR
until two years after start of study medication
Best response rate
Time Frame: until two years after start of study medication
Defined as the best observed response at any time point during observational period.
until two years after start of study medication
Duration of CRc
Time Frame: until two years after start of study medication
Defined as the number of days between the date of CR/CRi achievement and the date of the last assessment confirming CR/CRi
until two years after start of study medication
Duration of PR
Time Frame: until two years after start of study medication
Defined as the number of days between the date of PR achievement and the date of the last assessment confirming PR.
until two years after start of study medication
Progression free survival (PFS)
Time Frame: until two years after start of study medication
Is defined as the time from first treatment with GEM333 until disease progression or death from any cause
until two years after start of study medication
Overall survival
Time Frame: until two years after start of study medication
Defined as the number of days between the first study drug administration and death from any cause
until two years after start of study medication

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AvenCell Europe GmbH

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GCP-Service International Ltd. & Co. KG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Martin Wermke, MD, Universitätsklinikum Carl Gustav Carus Dresden

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 11, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 14, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 14, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 6, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GEM333-01
  • 2017-001707-77 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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