APG101 in Myelodysplastic Syndrome (APG101 in MDS)

This study is currently recruiting participants.
Verified March 2014 by Apogenix GmbH
Sponsor:
Information provided by (Responsible Party):
Apogenix GmbH
ClinicalTrials.gov Identifier:
NCT01736436
First received: November 14, 2012
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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

Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Treatment with APG101
Procedure: Bone marrow collection
Procedure: Blood drawings
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: APG101 in Transfusion-Dependent Patients With Low or Intermediate Risk Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Apogenix GmbH:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: During the whole study (37 weeks) ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: OS is captured for 37 weeks (during study) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    Changes in Hb level will be evaluated as those are early signs of an improval in erythropoiesis


Estimated Enrollment: 18
Study Start Date: January 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01736436

Contacts
Contact: Claudia Kunz, Dr. +49 6221 58608 0 claudia.kunz@apogenix.com
Contact: Harald Fricke, Dr. +49 6221 58608 0 harald.fricke@apogenix.com

Locations
Germany
Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie Recruiting
Heidelberg, Germany, 69120
Contact: Thomas Luft, MD    +49 6221 ext 56 0      
Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie Recruiting
Mannheim, Germany, 68167
Contact: Florian Nolte, MD    +49 621 ext 383 0      
Sponsors and Collaborators
Apogenix GmbH
Investigators
Principal Investigator: Florian Nolte, MD Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
  More Information

No publications provided

Responsible Party: Apogenix GmbH
ClinicalTrials.gov Identifier: NCT01736436     History of Changes
Other Study ID Numbers: APG101_CD_003, 2012-003027-37
Study First Received: November 14, 2012
Last Updated: March 11, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Apogenix GmbH:
MDS
Myelodysplastic syndrome
Low and intermediate risk
Transfusion-dependent patients
Transfusion
Anemia

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014