APG101 in Myelodysplastic Syndrome (APG101 in MDS)
Primary Purpose
Myelodysplastic Syndrome
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Treatment with APG101
Bone marrow collection
Blood drawings
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring MDS, Myelodysplastic syndrome, Low and intermediate risk, Transfusion-dependent patients, Transfusion, Anemia
Eligibility 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)
Sites / Locations
- Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie
- Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
100 mg APG101 weekly over 12 weeks
Arm Description
Single arm open label study. Patient receive 100 mg APG101 i.v. weekly over 12 weeks with a 6 monthly follow-up phase
Outcomes
Primary Outcome Measures
Safety and tolerability
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)
Overall survival (OS) is defined as time from start of study treatment to death from any cause
Changes in transfusion frequency
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
By assessing different parameters (cytologic, hematologic, cytogenetic), safety as well as efficacy of treatment with APG101 can be evaluated
Changes in hemoglobin (Hb) level
Changes in Hb level will be evaluated as those are early signs of an improval in erythropoiesis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01736436
Brief Title
APG101 in Myelodysplastic Syndrome
Acronym
APG101 in MDS
Official Title
APG101 in Transfusion-Dependent Patients With Low or Intermediate Risk Myelodysplastic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apogenix GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
MDS, Myelodysplastic syndrome, Low and intermediate risk, Transfusion-dependent patients, Transfusion, Anemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100 mg APG101 weekly over 12 weeks
Arm Type
Experimental
Arm Description
Single arm open label study. Patient receive 100 mg APG101 i.v. weekly over 12 weeks with a 6 monthly follow-up phase
Intervention Type
Drug
Intervention Name(s)
Treatment with APG101
Intervention Description
Patients will be treated 12 weeks with 100 mg APG101 intravenous weekly
Intervention Type
Procedure
Intervention Name(s)
Bone marrow collection
Intervention Description
During the study, bone marrow will be collected 4 times to assess study objectives
Intervention Type
Procedure
Intervention Name(s)
Blood drawings
Intervention Description
During the study, blood will be drawn at different time points to assess study objectives
Primary Outcome Measure Information:
Title
Safety and tolerability
Description
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.
Time Frame
During the whole study (37 weeks)
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Overall survival (OS) is defined as time from start of study treatment to death from any cause
Time Frame
OS is captured for 37 weeks (during study)
Title
Changes in transfusion frequency
Description
Changes in transfusion frequency will be evaluated as those are early signs of an improval in erythropoiesis
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)
Title
Changes of different parameters (e.g. histologic, cytologic, cytogenetic) in bone marrow according to Chesson criteria
Description
By assessing different parameters (cytologic, hematologic, cytogenetic), safety as well as efficacy of treatment with APG101 can be evaluated
Time Frame
During the study (37 weeks)
Title
Changes in hemoglobin (Hb) level
Description
Changes in Hb level will be evaluated as those are early signs of an improval in erythropoiesis
Time Frame
During the study (37 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Florian Nolte, MD
Organizational Affiliation
Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
12. IPD Sharing Statement
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APG101 in Myelodysplastic Syndrome
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