APG101 in Myelodysplastic Syndrome (APG101 in MDS)
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
Drug: Treatment with APG101
Procedure: Bone marrow collection
Procedure: Blood drawings
|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|
- 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.
- 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
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
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 weeklyProcedure: Bone marrow collection
During the study, bone marrow will be collected 4 times to assess study objectivesProcedure: Blood drawings
During the study, blood will be drawn at different time points to assess study objectives
Please refer to this study by its ClinicalTrials.gov identifier: NCT01736436
|Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie|
|Heidelberg, Germany, 69120|
|Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie|
|Mannheim, Germany, 68167|
|Principal Investigator:||Florian Nolte, MD||Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany|