Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03516760
Recruitment Status : Recruiting
First Posted : May 4, 2018
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
GCP-Service International Ltd. & Co. KG
Information provided by (Responsible Party):
GEMoaB Monoclonals GmbH

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Relapsed AML Refractory AML Drug: GEM333 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 11, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: GEM333
application of GEM333, a CD33 targeted bispecific antibody engaging T-cells
Drug: GEM333
infusion of GEM333; administered intravenously and continuously over 10 days




Primary Outcome Measures :
  1. 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.

  2. 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)

  3. Incidence and intensity of adverse events graded according to CTCAE V4.03 [ Time Frame: End of Treatment (EOT) +8 days resp. +28 days ]

Secondary Outcome Measures :
  1. 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). ]
    The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.

  2. Complete remission (CR) [ Time Frame: until two years after start of study medication ]
    bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L

  3. Composite complete remission (CRc) rate [ Time Frame: until two years after start of study medication ]
    Rate at any time point, defined as the proportion of patients having either CR or CRi

  4. Partial Remission (PR) [ Time Frame: until two years after start of study medication ]
    All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.

  5. Disease stabilization (DS) [ Time Frame: until two years after start of study medication ]
    Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR

  6. Best response rate [ Time Frame: until two years after start of study medication ]
    Defined as the best observed response at any time point during observational period.

  7. Duration of CRc [ Time Frame: until two years after start of study medication ]
    Defined as the number of days between the date of CR/CRi achievement and the date of the last assessment confirming CR/CRi

  8. Duration of PR [ Time Frame: until two years after start of study medication ]
    Defined as the number of days between the date of PR achievement and the date of the last assessment confirming PR.

  9. Progression free survival (PFS) [ Time Frame: until two years after start of study medication ]
    Is defined as the time from first treatment with GEM333 until disease progression or death from any cause

  10. Overall survival [ Time Frame: until two years after start of study medication ]
    Defined as the number of days between the first study drug administration and death from any cause



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03516760


Contacts
Layout table for location contacts
Contact: Martina Raupach +493514466450 ext 0 m.raupach@cellex-treatment.me
Contact: Jana Hase +493514466450 ext 0 j.hase@cellex-treatment.me

Locations
Layout table for location information
Germany
Universitätsmedizin Mannheim Recruiting
Mannheim, Baden-Württemberg, Germany, 68167
Contact: Stefan Klein, PD Dr.       stefan.klein@umm.de   
Principal Investigator: Stefan Klein, PD Dr.         
Klinikum rechts der Isar Recruiting
München, Bayern, Germany, 81675
Contact: Katharina Götze, Prof.       katharina.goetze@tum.de   
Principal Investigator: Katharina Götze, Prof.         
Universitätsklinikum Würzburg Recruiting
Würzburg, Bayern, Germany, 97080
Contact: Maria Elisabeth Goebeler, MD       Goebeler_M@ukw.de   
Principal Investigator: Götz-Ulrich Grigoleit, MD         
Universitätsklinikum Frankfurt Recruiting
Frankfurt am Main, Hessen, Germany, 60590
Contact: Björn Steffen, Dr.       steffen@em.uni-frankfurt.de   
Principal Investigator: Björn Steffen, Dr.         
Universitätsklinikum Marburg Recruiting
Marburg, Hessen, Germany, 35039
Contact: Stephan Metzelder, Dr.         
Universitätsklinikum Dresden Recruiting
Dresden, Sachsen, Germany, 01307
Contact: Martin Wermke, MD       martin.wermke@uniklinikum-dresden.de   
Principal Investigator: Martin Wermke, MD         
Charité Universitätsmedizin Recruiting
Berlin, Germany, 13353
Contact: Jörg Westermann, Prof.       joerg.westermann@charite.de   
Sponsors and Collaborators
GEMoaB Monoclonals GmbH
GCP-Service International Ltd. & Co. KG
Investigators
Layout table for investigator information
Principal Investigator: Martin Wermke, MD Universitätsklinikum Carl Gustav Carus Dresden

Layout table for additonal information
Responsible Party: GEMoaB Monoclonals GmbH
ClinicalTrials.gov Identifier: NCT03516760     History of Changes
Other Study ID Numbers: GEM333-01
2017-001707-77 ( EudraCT Number )
First Posted: May 4, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs