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

NCT03516760 | Terminated Phase 1 DMC

• 2 other identifiers: GEM333-012017-001707-77
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

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.

Conditions

Acute Myeloid Leukemia; Relapsed AML; Refractory AML

Outcome Measures

Primary Outcomes (3)

• 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)

• 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

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

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

Secondary Outcomes (10)

• 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).

• Complete remission (CR)

  until two years after start of study medication

• Composite complete remission (CRc) rate

  until two years after start of study medication

• Partial Remission (PR)

  until two years after start of study medication

• Disease stabilization (DS)

  until two years after start of study medication

Study Arms (1)

GEM333

EXPERIMENTAL

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

Drug: GEM333

Interventions

GEM333 DRUG

infusion of GEM333; administered intravenously and continuously over 10 days

GEM333

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, ≥ 18 years of age
• Documented definitive diagnosis of CD33 positive AML (according to standard of care testing) in
• a. 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)
• b. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AvenCell Europe GmbH: lead
• GCP-Service International Ltd. & Co. KG: collaborator

Study Sites (7)

Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Klinikum rechts der Isar

München, Bavaria, 81675, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Marburg

Marburg, Hesse, 35039, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Charité Universitätsmedizin

Berlin, 13353, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Martin Wermke, MD

  Universitätsklinikum Carl Gustav Carus Dresden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: May 4, 2018
• Study Start: April 11, 2018
• Primary Completion: June 14, 2022
• Study Completion: June 14, 2022
• Last Updated: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)