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APG101 in Myelodysplastic Syndrome (APG101 in MDS)

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ClinicalTrials.gov Identifier: NCT01736436
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : August 24, 2016
Sponsor:
Information provided by (Responsible Party):
Apogenix AG ( Apogenix GmbH )

Tracking Information
First Submitted Date  ICMJE November 14, 2012
First Posted Date  ICMJE November 29, 2012
Last Update Posted Date August 24, 2016
Study Start Date  ICMJE January 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2012)
Safety and tolerability [ Time Frame: During the whole study (37 weeks) ]
Evaluation of adverse events (AEs) and serious adverse events (SAEs). Evaluation of electrocardiograms (ECGs), abdominal ultrasound, anti-drug antibodies (ADA), changes in lymphocyte subpopulations / activation markers and changes in performance status (ECOG). Any side effects potentially related to the APG101 treatment are evaluated.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2012)
  • Overall survival (OS) [ Time Frame: OS is captured for 37 weeks (during study) ]
    Overall survival (OS) is defined as time from start of study treatment to death from any cause
  • Changes in transfusion frequency [ Time Frame: During the whole study. Baseline values are compared to values under treatment with APG101 (e.g baseline compared to week 12 and week 37) ]
    Changes in transfusion frequency will be evaluated as those are early signs of an improval in erythropoiesis
  • Changes of different parameters (e.g. histologic, cytologic, cytogenetic) in bone marrow according to Chesson criteria [ Time Frame: During the study (37 weeks) ]
    By assessing different parameters (cytologic, hematologic, cytogenetic), safety as well as efficacy of treatment with APG101 can be evaluated
  • Changes in hemoglobin (Hb) level [ Time Frame: During the study (37 weeks) ]
    Changes in Hb level will be evaluated as those are early signs of an improval in erythropoiesis
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APG101 in Myelodysplastic Syndrome
Official Title  ICMJE APG101 in Transfusion-Dependent Patients With Low or Intermediate Risk Myelodysplastic Syndrome
Brief Summary

It has been shown in preclinical experiments with bone marrow from patients with myelodysplastic syndrome that APG101 rescues erythrocytes from premature cell death. This is expected to translate in an improved erythropoiesis and ameliorated anemia in MDS patients.

APG101 might, therefore, be a valuable addition to current treatments of low- or intermediate MDS patients suffering from anaemia.

Transfusion-dependent patients with low or intermediate risk MDS according to WHO Prognostic Scoring Scale (WPSS) can be included in this study.

Treatment consists of 100mg APG101 intravenous as a weekly treatment over 12 weeks + 6 months follow up phase.

Primary objective of the trial is safety and tolerability of APG101; secondary objectives are

  • Hematologic, cytologic and cytogenetic response rate using modified International Working Group (IWG) response criteria
  • Incidence and time to leukemic progression at 37 weeks
  • OS (Overall survival) at 37 weeks
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: Treatment with APG101
    Patients will be treated 12 weeks with 100 mg APG101 intravenous weekly
  • Procedure: Bone marrow collection
    During the study, bone marrow will be collected 4 times to assess study objectives
  • Procedure: Blood drawings
    During the study, blood will be drawn at different time points to assess study objectives
Study Arms  ICMJE Experimental: 100 mg APG101 weekly over 12 weeks
Single arm open label study. Patient receive 100 mg APG101 i.v. weekly over 12 weeks with a 6 monthly follow-up phase
Interventions:
  • Drug: Treatment with APG101
  • Procedure: Bone marrow collection
  • Procedure: Blood drawings
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 23, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2012)
12
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent
  • Male and female patients with cytologically or histologically established diagnosis of de novo MDS according to the WHO-classification, either previously treated or untreated, presenting with low or intermediate risk features according to WHO prognostic status scale (WPSS)
  • Diagnosis of MDS with a medullary blast count of less than 5% has to be established or confirmed by bone marrow morphology
  • MDS with 5q deletion only if Lenalidomide is not a treatment option
  • Red blood cell transfusion dependency of at least 4 units of packed red blood cells (PRBC) during the last 8 weeks before inclusion. Only PRBC transfusions given for a Hb level ≤ 9g/dl or a haemoglobin level > 9g/dl, if clinically indicated (e.g. coronary heart disease, long distance travel), will count.
  • Patients refractory to Erythropoietin-stimulating agents (ESA) (as assessed after at least 8 weeks of treatment) or with a low possibility to respond to ESA treatment
  • at least 18 years old, smoking or non-smoking, of any ethnic origin
  • ECOG performance status ≤ 2
  • Suitable veins or existing port system for intra-venous infusion
  • Adequate contraception

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • MDS with medullary blast count ≥ 5%
  • Chronic monomyeloic leucemia (CMML)
  • Therapy-related / secondary MDS
  • High-risk karyotype according to WPSS
  • Patients scheduled for bone marrow or stem cell transplant within the next 6 months
  • Parallel treatment with ESA or with other experimental therapy
  • Prior chemotherapy (including Vidaza)
  • Treatment within the last 6 weeks with histone deacetylase (HDAC) inhibitors or ESAs
  • Treatment within any other clinical trial parallel to the treatment phase of the current study or within 30 days before inclusion
  • Active uncontrolled infection
  • HIV, active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection
  • Any other condition / treatment or past medical history of diseases with poor prognosis that, in the opinion of the investigator, might interfere with the study
  • History of or current drug or substance abuse
  • History of other (haemato-) oncological disease (except for non-melanoma skin cancer and adequately treated in situ carcinoma of the cervix)
  • Inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
  • Unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study
  • Subject is the investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
  • Hypersensitivity to recombinant proteins or excipients in the investigational drug
  • Pregnancy or breast feeding
  • Vulnerable patients (e.g., minors or persons kept in detention)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01736436
Other Study ID Numbers  ICMJE APG101_CD_003
2012-003027-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Apogenix AG ( Apogenix GmbH )
Study Sponsor  ICMJE Apogenix GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Florian Nolte, MD Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
PRS Account Apogenix AG
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP