- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03516760
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
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
36
Phase
- 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
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Berlin, Germany, 13353
- Charité Universitätsmedizin
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Baden-Württemberg
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Mannheim, Baden-Württemberg, Germany, 68167
- Universitätsmedizin Mannheim
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Bayern
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München, Bayern, Germany, 81675
- Klinikum rechts der Isar
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Würzburg, Bayern, Germany, 97080
- Universitätsklinikum Würzburg
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Hessen
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Frankfurt am Main, Hessen, Germany, 60590
- Universitatsklinikum Frankfurt
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Marburg, Hessen, Germany, 35039
- Universitätsklinikum Marburg
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Sachsen
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Dresden, Sachsen, Germany, 01307
- Universitätsklinikum Dresden
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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
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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)
- 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
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 |
Intervention / Treatment |
---|---|
Experimental: GEM333
application of GEM333, a CD33 targeted bispecific antibody engaging T-cells
|
infusion of GEM333; administered intravenously and continuously over 10 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose (MTD)
Time Frame: End of Treatment (EOT) +8 days resp. +28 days (DLT period)
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MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.
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End of Treatment (EOT) +8 days resp. +28 days (DLT period)
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Incidence of dose limiting toxicity (DLT)
Time Frame: End of Treatment (EOT) +8 days resp. +28 days
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Dose Limiting Toxicity is defined as any event at least possibly related to IMP (complete definition provided protocol)
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End of Treatment (EOT) +8 days resp. +28 days
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Incidence and intensity of adverse events graded according to CTCAE V4.03
Time Frame: End of Treatment (EOT) +8 days resp. +28 days
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End of Treatment (EOT) +8 days resp. +28 days
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Secondary Outcome Measures
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).
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The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
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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).
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Complete remission (CR)
Time Frame: until two years after start of study medication
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bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L
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until two years after start of study medication
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Composite complete remission (CRc) rate
Time Frame: until two years after start of study medication
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Rate at any time point, defined as the proportion of patients having either CR or CRi
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until two years after start of study medication
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Partial Remission (PR)
Time Frame: until two years after start of study medication
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All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.
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until two years after start of study medication
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Disease stabilization (DS)
Time Frame: until two years after start of study medication
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Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR
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until two years after start of study medication
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Best response rate
Time Frame: until two years after start of study medication
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Defined as the best observed response at any time point during observational period.
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until two years after start of study medication
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Duration of CRc
Time Frame: until two years after start of study medication
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Defined as the number of days between the date of CR/CRi achievement and the date of the last assessment confirming CR/CRi
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until two years after start of study medication
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Duration of PR
Time Frame: until two years after start of study medication
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Defined as the number of days between the date of PR achievement and the date of the last assessment confirming PR.
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until two years after start of study medication
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Progression free survival (PFS)
Time Frame: until two years after start of study medication
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Is defined as the time from first treatment with GEM333 until disease progression or death from any cause
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until two years after start of study medication
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Overall survival
Time Frame: until two years after start of study medication
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Defined as the number of days between the first study drug administration and death from any cause
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until two years after start of study medication
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Martin Wermke, MD, Universitatsklinikum 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)
April 11, 2018
Primary Completion (Actual)
June 14, 2022
Study Completion (Actual)
June 14, 2022
Study Registration Dates
First Submitted
April 6, 2018
First Submitted That Met QC Criteria
May 3, 2018
First Posted (Actual)
May 4, 2018
Study Record Updates
Last Update Posted (Actual)
September 29, 2022
Last Update Submitted That Met QC Criteria
September 28, 2022
Last Verified
September 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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