Myelodysplastic SyndromePhase 1APG101 in MDSNCT01736436
APG101 in Myelodysplastic Syndrome
A Phase 1 study testing Treatment with APG101, Bone marrow collection and Blood drawings in people with Myelodysplastic Syndrome, run by Apogenix GmbH at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Treatment with APG101, Bone marrow collection and Blood drawings
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesGermany
- Study dates
- Jan 2013to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 21Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie
Heidelberg, 69120
Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie
Mannheim, 68167
About this study
Official title: APG101 in Transfusion-Dependent Patients With Low or Intermediate Risk Myelodysplastic Syndrome
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.
Read more
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
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Treatment with APG101, Bone marrow collection, Blood drawings
- Keywords
- MDS, Myelodysplastic syndrome, Low and intermediate risk, Transfusion-dependent patients, Transfusion, Anemia
- Medical subject headings
- Myelodysplastic Syndromes, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with APG101Drug
Patients will be treated 12 weeks with 100 mg APG101 intravenous weekly
Bone marrow collectionProcedure or surgery
During the study, bone marrow will be collected 4 times to assess study objectives
Blood drawingsProcedure or surgery
During the study, blood will be drawn at different time points to assess study objectives
| Study group | Role | What they receive |
|---|---|---|
| 100 mg APG101 weekly over 12 weeks | Experimental | Single arm open label study. Patient receive 100 mg APG101 i.v. weekly over 12 weeks with a 6 monthly follow-up phase Receives: Drug: Treatment with APG101; Procedure: Bone marrow collection; Procedure: Blood drawings |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the whole study (37 weeks)
Secondary outcomes (4)
Overall survival (OS)
Overall survival (OS) is defined as time from start of study treatment to death from any cause
Measured: OS is captured for 37 weeks (during study)
Changes in transfusion frequency
Changes in transfusion frequency will be evaluated as those are early signs of an improval in erythropoiesis
Measured: 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 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
Measured: During the study (37 weeks)
Changes in hemoglobin (Hb) level
Changes in Hb level will be evaluated as those are early signs of an improval in erythropoiesis
Measured: During the study (37 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Apogenix GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Florian Nolte, MD, Principal investigator, Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01736436
- Sponsor's protocol ID
- APG101_CD_003
- Other IDs
- 2012-003027-37
- Acronym
- APG101 in MDS
- Status last verified
- Aug 2016
- First submitted
- 14 Nov 2012
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- APG101 in Transfusion-Dependent Patients With Low or Intermediate Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT01736436
- Acronym / sponsor ID
- APG101 in MDS / APG101_CD_003
- Conditions
- Myelodysplastic Syndrome
- Keywords
- MDS, Myelodysplastic syndrome, Low and intermediate risk, Transfusion-dependent patients, Transfusion, Anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Apogenix GmbHIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 29 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 100 mg APG101 weekly over 12 weeks | Experimental | Drug: Treatment with APG101, Procedure: Bone marrow collection, Procedure: Blood drawingsSingle arm open label study. Patient receive 100 mg APG101 i.v. weekly over 12 weeks with a 6 monthly follow-up phase |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment with APG101Patients will be treated 12 weeks with 100 mg APG101 intravenous weekly | Drug | 100 mg APG101 weekly over 12 weeks |
| Bone marrow collectionDuring the study, bone marrow will be collected 4 times to assess study objectives | Procedure or surgery | 100 mg APG101 weekly over 12 weeks |
| Blood drawingsDuring the study, blood will be drawn at different time points to assess study objectives | Procedure or surgery | 100 mg APG101 weekly over 12 weeks |
Primary outcome
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.
4 secondary outcomes
Overall survival (OS)
Time frame: OS is captured for 37 weeks (during study)
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 of different parameters (e.g. histologic, cytologic, cytogenetic) in bone marrow according to Chesson criteria
Time frame: During the study (37 weeks)
Changes in hemoglobin (Hb) level
Time frame: During the study (37 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florian Nolte, MD principal investigator
Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treatment with APG101, Bone marrow collection and Blood drawings in people with Myelodysplastic Syndrome, run by Apogenix GmbH at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (time frame: During the whole study (37 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2016.