APG101 in Myelodysplastic Syndrome

NCT01736436 | Completed Phase 1

• 2 other identifiers: APG101_CD_0032012-003027-37
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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

Conditions

Myelodysplastic Syndrome

Keywords

MDS; Myelodysplastic syndrome; Low and intermediate risk; Transfusion-dependent patients; Transfusion; Anemia

Outcome Measures

Primary Outcomes (1)

• 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.

  During the whole study (37 weeks)

Secondary Outcomes (4)

• Overall survival (OS)

  OS is captured for 37 weeks (during study)

• Changes in transfusion frequency

  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

  During the study (37 weeks)

• Changes in hemoglobin (Hb) level

  During the study (37 weeks)

Study Arms (1)

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

Drug: Treatment with APG101; Procedure: Bone marrow collection; Procedure: Blood drawings

Interventions

Treatment with APG101 DRUG

Patients will be treated 12 weeks with 100 mg APG101 intravenous weekly

100 mg APG101 weekly over 12 weeks

Bone marrow collection PROCEDURE

During the study, bone marrow will be collected 4 times to assess study objectives

100 mg APG101 weekly over 12 weeks

Blood drawings PROCEDURE

During the study, blood will be drawn at different time points to assess study objectives

100 mg APG101 weekly over 12 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Apogenix GmbH: lead

Study Sites (2)

Universitaetsklinik Heidelberg, Medizinische Klinik V, Haematologie, Onkologie & Rheumatologie

Heidelberg, 69120, Germany

Location

Universitaetsmedizin Mannheim, III. Medizinische Klinik, Haematologie und Onkologie

Mannheim, 68167, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

Therapeutics; APG101

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Florian Nolte, MD

  Universitaetsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und Onkologie, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2012
• First Posted: November 29, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

DE (2)