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

AvenCell Europe GmbH7 sites in 1 country36 target enrollmentApril 11, 2018

ConditionsAcute Myeloid Leukemia Relapsed AML Refractory AML

InterventionsGEM333

DrugsGEM333

Overview

Phase: Phase 1
Intervention: GEM333
Conditions: Acute Myeloid Leukemia
Sponsor: AvenCell Europe GmbH
Enrollment: 36
Locations: 7
Primary Endpoint: Incidence of dose limiting toxicity (DLT)
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

April 11, 2018

End Date

June 14, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

AvenCell Europe GmbH

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

GEM333

application of GEM333, a CD33 targeted bispecific antibody engaging T-cells

Intervention: GEM333

Outcomes

Primary Outcomes

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)

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

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

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.

Secondary Outcomes

Composite complete remission (CRc) rate(until two years after start of study medication)
Overall survival(until two years after start of study medication)
Complete remission (CR)(until two years after start of study medication)
Partial Remission (PR)(until two years after start of study medication)
Best response rate(until two years after start of study medication)
Recommended phase 2 dose(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).)
Disease stabilization (DS)(until two years after start of study medication)
Duration of CRc(until two years after start of study medication)
Duration of PR(until two years after start of study medication)
Progression free survival (PFS)(until two years after start of study medication)