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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

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
• 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
• 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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory AML
• Relapsed AML

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