APG101 in Myelodysplastic Syndrome (APG101 in MDS)

Apogenix

Status and phase

Completed

Phase 1

Conditions

Myelodysplastic Syndrome

Treatments

Procedure: Bone marrow collection

Procedure: Blood drawings

Drug: Treatment with APG101

Study type

Interventional

Funder types

Industry

Identifiers

NCT01736436

APG101_CD_003

2012-003027-37 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)