Prevention of Acute Graft Versus Host Disease in Patients Undergoing Allogeneic ApoGraft Stem Cell Transplantation

An Open-Label Phase I/II, Pilot, Staggered Four-Cohort Safety and Proof-of-Concept Study of ApoGraft in the Prevention of Acute Graft Versus Host Disease (aGvHD)

Interventional, open label, Phase I/II, Safety and Proof-of-Concept Study, with a follow up period of 180 days after the transplantation of ApoGraft.

ApoGraft product is a mobilized peripheral blood cell product of a matched Related donor, collected via apheresis, which is exposed to the apoptotic mediator Fas Ligand (CD95L) prior to transplantation (Ex Vivo).

The study is designed to address the aspects of engraftment and Prevention of Acute Graft versus Host Disease (aGvHD) rate and/or severity in 12 Patients

STUDY DESIGN:

This is a phase 1/2, open-label, proof-of-concept, staggered 4-cohort clinical study. Each cohort will include 3 patients with hemato-oncology disorders eligible for allogeneic HLA-matched HSCT. Patients in all cohorts will undergo similar study procedures and evaluation. The cohorts will differ from each other in the amount of apoptotic mediator Fas Ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT, ranging from 10 ng/ml APO010 in Cohort 1, 25 ng/ml APO010 in Cohort 2, 50 ng/ml APO010 in Cohort 3 and 100 ng/ml APO010 in Cohort 4. APO010 is washed-out as part of the ApoGraft process and only trace amounts of APO010 are present in the final ApoGraft product

The study consists of a screening phase (subject and donor clinical assessment and screening tests), transplantation of ApoGraft, and a follow-up period of 180 days during and after hospitalization.

The study will progress from one cohort to the next based on an independent data safety monitoring board (DSMB) review and analysis of safety data

Recipient/patient main inclusion criteria:

1. Adult male or female subjects, 18-70 years of age.

2. Subjects are eligible for allogeneic HLA-matched related HSCT for any hematological malignancies for which transplantation is appropriate with corresponding related donor. One of the following hemato-oncology disorders diagnosis is required:

   • Acute myelogenous leukemia (AML) and Acute lymphoblastic leukemia (ALL) in 1st or subsequent complete remission (CR)
   • Non-Hodgkin's disease (NHD) in CR by CT or PET/CT
   • Hodgkin's disease (HD) in 1st or subsequent CR by CT or PET/CT
   • Intermediate, High or Very High Risk Myelodysplastic syndrome (MDS) (IPSS-R criteria)

3. The donor and recipient must have full match at the HLA A, B, C, DR and DQ loci.

4. ECOG performance status score 0-1 at time of the screening visit.

5. Subjects must have adequate organ function as defined in the study protocol

6. Signed written informed consent to participate in the study.

7. If female of childbearing potential, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test.

Donor main inclusion criteria:

1. Adult male or female subjects, 18-65 years of age.
2. Donor criteria according to standard WMDA criteria for donor selection. 3 Must have full match at the HLA A, B, C, DR and DQ loci with the recipient.

4. Signed written informed consent

Recipient/patient main exclusion criteria:

1. Use of non-myeloabletive conditioning.
2. Uncontrolled infections including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis within two weeks of the screening visit.
3. Current known acute or chronic infection with HBV or HCV.
4. Known human immunodeficiency virus (HIV) infection or AIDS.
5. Subjects with severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support.
6. Subjects with other concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study (i.e. active infection, uncontrolled diabetes, uncontrolled hypertension, congestive cardiac failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months and chronic liver or renal disease.
7. Any form of substance abuse (including drug or alcohol abuse), psychiatric disorder or any chronic condition susceptible, in the opinion of the investigator, of interfering with the conduct of the study.
8. Organ allograft or previous history of allogeneic stem cell transplantation.
9. Pregnancy or lactation.

Donor main exclusion criteria:

1. HIV, HBV or HCV positive subjects.
2. Pregnant or lactating women.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.