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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03516760
Other study ID # GEM333-01
Secondary ID 2017-001707-77
Status Terminated
Phase Phase 1
First received
Last updated
Start date April 11, 2018
Est. completion date June 14, 2022

Study information

Verified date September 2022
Source AvenCell Europe GmbH
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


Recruitment information / eligibility

Status Terminated
Enrollment 36
Est. completion date June 14, 2022
Est. primary completion date June 14, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
GEM333
infusion of GEM333; administered intravenously and continuously over 10 days

Locations

Country Name City State
Germany Charité Universitätsmedizin Berlin
Germany Universitätsklinikum Dresden Dresden Sachsen
Germany Universitätsklinikum Frankfurt Frankfurt am Main Hessen
Germany Universitätsmedizin Mannheim Mannheim Baden-Württemberg
Germany Universitätsklinikum Marburg Marburg Hessen
Germany Klinikum rechts der Isar München Bayern
Germany Universitätsklinikum Würzburg Würzburg Bayern

Sponsors (2)

Lead Sponsor Collaborator
AvenCell Europe GmbH GCP-Service International Ltd. & Co. KG

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (MTD) 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)
Primary Incidence of dose limiting toxicity (DLT) 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
Primary Incidence and intensity of adverse events graded according to CTCAE V4.03 End of Treatment (EOT) +8 days resp. +28 days
Secondary 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. 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).
Secondary Complete remission (CR) 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
Secondary Composite complete remission (CRc) rate Rate at any time point, defined as the proportion of patients having either CR or CRi until two years after start of study medication
Secondary 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 %. until two years after start of study medication
Secondary 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 until two years after start of study medication
Secondary Best response rate Defined as the best observed response at any time point during observational period. until two years after start of study medication
Secondary 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 until two years after start of study medication
Secondary Duration of PR 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
Secondary Progression free survival (PFS) 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
Secondary Overall survival 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
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