An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
Phase: PHASE2
Conditions: Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome
Sponsor: Kiadis Pharma

Clinical Study Protocol: CR-AIR-008 
Study Title: 
An exploratory, open-label, multicenter study to evaluate the safety 
and efficacy of a two-dose regimen of ATIR101, a T-lymphocyte 
enriched leukocyte preparation depleted ex vivo of host alloreactive 
T-cells (using photodynamic treatment), in patients with a 
hematologic malignancy, who received a CD34-selected 
hematopoietic stem cell transplantation from a haploidentical donor 
Study Number: 
CR-AIR-008 
Study Phase: 
Phase II 
Product Name: 
ATIR101 (previously referred to as ATIR) 
EudraCT Number: 
2015-002821-20 
Indication: 
Prevention of complications, such as infections and GvHD, and/or 
relapse after a haploidentical allogeneic hematopoietic stem cell 
transplantation 
Coordinating 
Investigators: 
Prof. Denis Claude Roy, MD  
Research Center and Cellular Therapy Laboratory 
Maisonneuve-Rosemont Hospital (Montreal, Canada) 
 
Prof. Dr. med. Stephan Mielke 
Allogeneic Stem Cell Transplant Center 
Julius Maximilian University of Würzburg (Würzburg, Germany) 
Sponsor: 
Kiadis Pharma 
Sponsor Contact: 
Karen Reitsma, PhD 
Director Clinical Operations 
Kiadis Pharma Netherlands B.V. (Amsterdam, The Netherlands) 
Phone: +31-20-314-0250 
E-mail: k.reitsma@kiadis.com 
 
 
 
Date 
Original Protocol: 
9 July 2015 
Amendment 1: 
20 November 2015 
 
 
Confidentiality Statement 
Information contained in this document is the property of Kiadis Pharma Netherlands B.V., and is 
confidential. This information may not be disclosed to third parties without written authorization from 
Kiadis Pharma Netherlands B.V., except to obtain informed consent from those persons to whom the 
product will be administered, and to comply with legal regulations. No part of this document may be 
reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, 
mechanical, recording or otherwise – without the prior authorization of Kiadis Pharma Netherlands B.V. 

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SYNOPSIS 
Sponsor: 
Kiadis Pharma 
Name of Finished Product: 
ATIR101 (previously referred to as ATIR) 
Name of Active Ingredient: 
ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host 
alloreactive T-cells (using photodynamic treatment) 
Study Title: 
An exploratory, open-label, multicenter study to evaluate the safety and efficacy of a two-
dose regimen of ATIR101, a T-lymphocyte enriched leukocyte preparation depleted ex vivo 
of host alloreactive T-cells (using photodynamic treatment), in patients with a hematologic 
malignancy, who received a CD34-selected hematopoietic stem cell transplantation from a 
haploidentical donor 
Study Number: 
CR-AIR-008 
Study Phase:  
Phase II 
Study Objective: 
To study the safety and efficacy of a repeat dose administration of ATIR101 in patients with 
a hematologic malignancy who received a T-cell depleted haploidentical hematopoietic stem 
cell transplantation (HSCT). 
Study Design: 
Study CR-AIR-008 is an exploratory, open-label, multicenter study. After signing informed 
consent, patients will receive an HSCT from a related, haploidentical donor, followed by a 
first ATIR101 infusion at a dose of 2×106 viable T-cells/kg between 28 and 32 days after the 
HSCT. Patients will receive a second ATIR101 infusion at a dose of 2×106 viable T-cells/kg 
between 70 and 74 days after the HSCT.  
To evaluate safety of the second dose administration, the first 6 patients treated will be 
evaluated for the occurrence of dose-limiting toxicity (DLT), defined as acute GvHD grade 
III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in 
case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the 
remaining 9 patients will continue with two ATIR101 doses of 2×106 viable T-cells/kg. If 
within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be 
adjusted to a dose of 1×106 viable T-cells/kg. If in one of the next 3 patients treated at this 
lower dose again DLT is observed, the second ATIR101 infusion will be halted and the 
remaining patients will be given only a single dose of ATIR101.  
All patients treated with ATIR101 will be followed up until 12 months after the HSCT. 

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Assessments will be performed at weekly visits from the day of the first ATIR101 infusion 
(Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 
4 until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT. 
Study Population:  
In total, 15 patients with a hematologic malignancy who are eligible for a haploidentical 
HSCT will be treated with two doses of ATIR101 (unless the second dose is halted for safety 
reasons).  
• Any of the following hematologic malignancies: 
Patient inclusion criteria 
- 
Acute myeloid leukemia (AML) in first remission with high-risk features or in second 
or higher remission 
- 
Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in 
second or higher remission 
- 
Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher 
IPSS-R risk group 
• Karnofsky performance status ≥ 70% 
• Eligible for haploidentical stem cell transplantation according to the investigator 
• Male or female, age ≥ 18 years and ≤ 65 years 
• Availability of a fully matched related or unrelated donor following a donor search 
Patient exclusion criteria 
• Diffusing capacity for carbon monoxide (DLCO) < 50% predicted 
• Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA) 
• AST > 2.5 x ULN (CTCAE grade 2) 
• Bilirubin > 1.5 x ULN (CTCAE grade 2) 
• Creatinine clearance < 50 mL/min (calculated or measured) 
• Positive HIV test  
• Positive pregnancy test (women of childbearing age only) 
• Prior allogeneic HSCT 
• Estimated probability of surviving less than 3 months 
• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide) 
• Known presence of HLA antibodies against the non-shared donor haplotype 
• Any other condition which, in the opinion of the investigator, makes the patient ineligible 
for the study 
• Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of 
the unshared haplotype 
Donor inclusion criterion 
• Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for 
donors under the age of 18 will be followed) 
• Eligible for donations of human blood and blood components according to local 
requirements and regulations 
• Eligible for donation according to the transplantation center 
 

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• Positive pregnancy test or nursing (women of childbearing age only) 
Donor exclusion criteria 
• Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV-1 (if 
tested), HTLV-2 (if tested), or WNV (if tested) 
Hematopoietic Stem Cell Transplantation (HSCT): 
In order to prepare the patient for the HSCT one of the following conditioning regimens is 
recommended. 
• Fractionated total body irradiation (TBI); 200 cGy twice daily for 3 days on Day -10 to -8 
(1200 cGy in 6 fractions) 
TBI regimen 
• Fludarabine; 30 mg/m2 intravenously (IV) once daily for 5 days on Day -7 to -3 
• Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 
• Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on 
Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients 
will receive methylprednisolone 2 mg/kg/day IV. 
• Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 
Non-TBI regimen 
• Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 
• Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 
• ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a 
continuous IV infusion for 8 hours. During the course of ATG, patients will receive 
methylprednisolone 2 mg/kg/day IV. 
 
The collection and preparation of the donor stem cell graft is performed according to 
institutional procedures at the study center. The study centers will mobilize peripheral blood 
stem cells (PBSCs) from the donor with granulocyte colony-stimulating factor (G-CSF) 
administered subcutaneously at a dose of approx. 8 µg/kg twice daily for approx. 4 to 7 days. 
The PBSCs will be collected by apheresis. According to the Perugia protocol for 
haploidentical transplants, the CD34-selected stem cell graft is targeted to contain at least 
5×106 CD34+ cells/kg but if possible 8-11×106 CD34+ cells/kg with a maximum of 3×104 
CD3+ cells/kg as assessed by flow cytometry. To ensure a consistently highly purified stem 
cell graft, clinical sites will use the CliniMACS® CD34 isolation system (from Miltenyi 
Biotec) as part of their institutional procedures for preparing the stem cell graft. 
Post-transplantation immunosuppressive therapy (e.g. corticosteroids) in the absence of 
GvHD should be avoided unless medically indicated. To prevent infections with 
cytomegalovirus (CMV), patients who are CMV positive or have a CMV positive donor will 
receive prophylactic treatment, and all patients will be subject to regular quantitative PCR 
monitoring followed by adequate (pre-emptive) treatment if indicated. 
To prevent infections with Epstein-Barr virus (EBV), patients who are EBV positive or have 
an EBV positive donor will be subject to regular quantitative PCR monitoring followed by 
adequate (pre-emptive) treatment if indicated. 

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Investigational Medicinal Product, Dose, and Mode of Administration:  
ATIR101, a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host 
alloreactive T-cells (using photodynamic treatment), will be cryopreserved until infusion to 
the patient. ATIR101 will be infused intravenously at a dose of 2×106 viable T-cells/kg body 
weight between 28 and 32 days after the HSCT (or later if required by the patient's medical 
condition). If not halted for safety reasons, patients will receive a second ATIR101 infusion 
between 70 and 74 days after the HSCT but at least 42 days after the first ATIR101 infusion 
(or later if required by the patient's medical condition). The second ATIR101 infusion will 
consist of a dose of 2×106 viable T-cells/kg (or an adjusted dose of 1×106 viable T-cells/kg 
when required). 
ATIR101 will not be infused at the time of the planned infusion if: 
• The patient is suffering from active GvHD (any grade), and/or 
• The patient is receiving steroid-based immunosuppressive therapy. 
Duration of Treatment and Study:  
ATIR101 will be administered as two intravenous infusions at 28-32 days and 70-74 days 
after the HSCT, respectively. Patients treated with ATIR101 will be followed up until 
12 months after the HSCT.  
The study is anticipated to be conducted between October 2015 and June 2017. 
Assessments: 
• GvHD assessment: 
- 
Occurrence and severity of acute and chronic GvHD 
• Mortality:  
- 
Occurrence of death, cause of death 
• Disease assessment:  
- 
Occurrence of relapse or disease progression 
• Infection assessment:  
- 
Occurrence and severity of viral, fungal, and bacterial infections, including viral 
reactivations 
• Immune reconstitution:  
- 
Total lymphocytes and immunophenotyping on peripheral blood as measured by flow 
cytometry: CD3+ (T-cells), CD3+ CD8+ (cytotoxic T-cells), CD3+ CD4+ (helper 
T-cells), CD3- CD56+ (NK-cells), and CD19+ (B-cells) 
- 
Immunoglobulins in peripheral blood: IgG, IgA, IgM 
 
Statistical Methods:  
• Incidence of acute graft versus host disease (GvHD) grade III/IV up to 180 days post 
HSCT. Thus, the primary analysis will be based on the data at 180 days after the HSCT. 
Primary endpoint (safety) 
• Incidence and severity of acute and chronic graft versus host disease (GvHD)  
Secondary endpoints (safety and efficacy) 
• Time to T-cell reconstitution, defined as the time to CD3+ in peripheral blood higher than 

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0.2×109/L (at two consecutive measurements; time to first measurement) 
• Incidence and severity of viral, fungal, and bacterial infections 
• Transplant-related mortality (TRM), defined as death due to causes other than disease 
relapse or progression, or other causes which are unrelated to the transplantation 
procedure (e.g. accident, suicide) 
• Relapse-related mortality (RRM), defined as death due to disease relapse or disease 
progression 
• Overall survival (OS), defined as the time from HSCT until death from any cause 
• Progression-free survival (PFS), defined as the time from HSCT until relapse, disease 
progression, or death, whichever occurs first 
• GvHD-free, relapse-free survival (GRFS), defined as the time until acute GvHD 
grade III/IV, chronic GvHD requiring systemic treatment, relapse, or death, whichever 
occurs first 
 
All endpoints will be analyzed using descriptive statistics. Immune reconstitution will be 
graphically displayed in time. The Kaplan-Meier method will be used to display and estimate 
probability of time-related survival data (OS, PFS, GRFS). In addition, cumulative incidence 
curves taking into account competing risks will be used to display and estimate cumulative 
incidences of TRM, RRM, and GvHD.  
Date of Original Approved Protocol:  
9 July 2015 
Date of Most Recent Protocol Amendment: 
20 November 2015 (Amendment 1) 
Prepared in:  
Microsoft Word 2007 

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TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................2 
TABLE OF CONTENTS ...........................................................................................................7 
LIST OF APPENDICES ............................................................................................................9 
LIST OF IN-TEXT TABLES ..................................................................................................10 
LIST OF IN-TEXT FIGURES.................................................................................................10 
LIST OF ABBREVIATIONS ..................................................................................................11 
1 
INTRODUCTION ...........................................................................................................15 
2 
STUDY OBJECTIVE ......................................................................................................19 
3 
INVESTIGATIONAL PLAN ..........................................................................................20 
3.1 
Overall Study Design and Plan ..............................................................................20 
3.2 
Rationale for Study Design ....................................................................................20 
3.3 
Study Duration .......................................................................................................20 
4 
STUDY POPULATION SELECTION ...........................................................................21 
4.1 
Study Population ....................................................................................................21 
4.2 
Patient Inclusion Criteria .......................................................................................21 
4.3 
Patient Exclusion Criteria ......................................................................................21 
4.4 
Donor Inclusion Criteria ........................................................................................22 
4.5 
Donor Exclusion Criteria .......................................................................................22 
5 
STUDY TREATMENT ...................................................................................................23 
5.1 
Description of Treatment .......................................................................................23 
5.1.1 
Hematopoietic Stem Cell Transplantation ...................................................23 
5.1.2 
Investigational Medicinal Product (ATIR101) ............................................23 
5.2 
Treatments Administered .......................................................................................25 
5.3 
Selection and Timing of Dose for Each Patient .....................................................26 
5.4 
Method of Assigning Patients to Treatment Groups..............................................27 
5.5 
Blinding..................................................................................................................27 
5.6 
Concomitant Therapy.............................................................................................27 
5.6.1 
Immunosuppressives ....................................................................................27 
5.6.2 
Hematopoietic Growth Factors ....................................................................27 
5.6.3 
Donor Lymphocyte Infusions (DLIs) ..........................................................28 
5.6.4 
Anti-viral Drugs ...........................................................................................28 
5.6.4.1 
Cytomegalovirus (CMV) ...................................................................28 
5.6.4.2 
Epstein-Barr Virus (EBV)..................................................................28 
5.6.4.3 
Herpes Simplex Virus (HSV) ............................................................29 
5.6.4.4 
Varicella Zoster Virus (VZV) ............................................................29 
5.6.5 
Anti-bacterial, Anti-parasitic, and Anti-fungal Drugs .................................29 

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5.7 
Treatment Compliance ...........................................................................................29 
5.8 
Packaging and Labeling .........................................................................................29 
5.9 
Storage and Accountability ....................................................................................30 
6 
STUDY PROCEDURES .................................................................................................31 
6.1 
Informed Consent...................................................................................................31 
6.2 
Patient Characteristics and Eligibility ....................................................................31 
6.3 
Donor Characteristics and Eligibility.....................................................................32 
6.4 
Vital Signs ..............................................................................................................33 
6.5 
Safety Laboratory Tests .........................................................................................33 
6.6 
Efficacy and Safety Assessments...........................................................................35 
6.6.1 
Immune Reconstitution ................................................................................35 
6.6.2 
Infection Assessment ...................................................................................36 
6.6.3 
Disease Assessment .....................................................................................36 
6.6.4 
Graft versus Host Disease Assessment ........................................................36 
6.6.5 
Mortality ......................................................................................................37 
6.7 
Adverse Events ......................................................................................................37 
6.8 
Serious Adverse Events .........................................................................................40 
6.9 
Concomitant Medication Assessments ..................................................................41 
6.10 
Discontinuation of Patients from the Study ...........................................................41 
7 
STUDY ASSESSMENTS BY VISIT ..............................................................................43 
7.1 
Screening: Between Informed Consent and Apheresis ..........................................43 
7.2 
HSCT (Day 0) ........................................................................................................44 
7.3 
Week 1, Week 2, and Week 3 ................................................................................44 
7.4 
First ATIR101 Infusion (Week 4) ..........................................................................45 
7.5 
Week 5, Week 6, Week 7, Week 8, and Week 9 ...................................................45 
7.6 
Second ATIR101 Infusion (Week 10) ...................................................................46 
7.7 
Week 11, Week 12, Week 13, Week 14, Week 15, and Week 16 .........................47 
7.8 
Month 5, Month 6, Month 9, and Month 12 ..........................................................48 
7.9 
End of Study ..........................................................................................................49 
8 
QUALITY CONTROL AND ASSURANCE .................................................................50 
8.1 
ATIR101 Manufacturing .......................................................................................50 
8.2 
Clinical Study.........................................................................................................50 
9 
PLANNED STATISTICAL METHODS ........................................................................51 
9.1 
General Considerations ..........................................................................................51 
9.2 
Determination of Sample Size ...............................................................................51 
9.3 
Analysis Populations ..............................................................................................51 
9.4 
Demographics and Baseline Characteristics ..........................................................52 
9.5 
Primary Endpoint (Safety) .....................................................................................52 

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9.6 
Secondary Endpoints .............................................................................................52 
10 ADMINISTRATIVE CONSIDERATIONS ....................................................................54 
10.1 
Independent Ethics Committee (IEC) Approval ....................................................54 
10.2 
Ethical Conduct of the Study .................................................................................54 
10.3 
Patient and Donor Information and Consent .........................................................54 
10.4 
Patient Confidentiality ...........................................................................................55 
10.5 
Study Monitoring ...................................................................................................56 
10.6 
Electronic Case Report Forms and Study Records ................................................56 
10.7 
Independent Data Monitoring Committee .............................................................57 
10.8 
Adjudication Committees ......................................................................................57 
10.9 
Major Protocol Deviations .....................................................................................57 
10.10 Access to Source Documentation ..........................................................................58 
10.11 Data Generation and Analysis ...............................................................................58 
10.12 Retention of Data ...................................................................................................58 
10.13 Financial Disclosure...............................................................................................58 
10.14 Publication and Disclosure Policy .........................................................................58 
11 REFERENCE LIST .........................................................................................................60 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Study Assessments ...................................................................... 63 
Appendix 2 
EBMT Risk Score ........................................................................................... 66 
Appendix 3 
Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) . 67 
Appendix 4 
Karnofsky Performance Status (KPS) Scale ................................................... 68 
Appendix 5 
Classification of Graft versus Host Disease (GvHD) ..................................... 69 
Appendix 6 
Adverse Events Not to Be Reported in the Electronic Case Report Form When 
Occurring Before ATIR101 Infusion .............................................................. 73 
Appendix 7 
Sponsor Signature ........................................................................................... 74 
Appendix 8 
Investigator’s Signature .................................................................................. 75 
 

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LIST OF IN-TEXT TABLES 
Table 1  
List of safety laboratory tests .......................................................................... 33 
Table 2 
Organ scoring of chronic GvHD ..................................................................... 70 
 
LIST OF IN-TEXT FIGURES 
Figure 1 
Schematic overview of the ATIR101 procedure ............................................ 25 
 

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LIST OF ABBREVIATIONS 
AE 
adverse event 
ALL 
acute lymphoblastic leukemia 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AP 
alkaline phosphatase 
AST 
aspartate aminotransferase 
ATG 
anti-thymocyte globulin 
BID 
twice daily 
cGy 
centigray 
CMP 
clinical monitoring plan 
CMV 
cytomegalovirus 
CNS 
central nervous system 
CRO 
contract research organization 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLCO 
diffusing capacity of the lung for carbon monoxide 
DLI 
donor lymphocyte infusion 
DLT 
dose-limiting toxicity 
DMP 
data management plan 
DMSO 
dimethylsulfoxide 
DNA 
deoxyribonucleic acid 
EBMT 
European Society for Blood and Marrow Transplantation 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
ENT 
ears, nose, throat 

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FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GMP 
Good Manufacturing Practice 
GRFS 
GvHD-free, relapse-free survival 
GvHD 
graft versus host disease 
GvL 
graft versus leukemia 
HBV 
hepatitis B virus 
HCT-CI 
hematopoietic cell transplantation-specific comorbidity index 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HSCT 
hematopoietic stem cell transplantation 
HSV 
herpes simplex virus 
HTLV 
human T-lymphotropic virus 
ICH 
International Conference on Harmonization 
IDMC 
independent data monitoring committee 
IEC 
independent ethics committee 
Ig 
immunoglobulin 
IMP 
investigational medicinal product 
IPSS-R 
Revised International Prognostic Scoring System 
ITT 
intention-to-treat 
IV 
intravenous(ly) 
KPS 
Karnofsky Performance Scale 
LDH 
lactate dehydrogenase 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
major histocompatibility complex 
MITT  
modified intention-to-treat 

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MLR 
mixed lymphocyte reaction 
MUGA 
multiple gated acquisition 
NAT 
nucleic acid test 
NCI 
National Cancer Institute 
NK 
natural killer (cells) 
OS 
overall survival 
PBSC 
peripheral blood stem cell 
PCR 
polymerase chain reaction 
PDT 
photodynamic treatment 
PFS 
progression-free survival 
PFT 
pulmonary function test 
PO 
orally 
PP 
per protocol 
PTLD 
post transplant lymphoproliferative disease 
q12h 
each 12 hours 
q24h 
each 24 hours 
QA 
Quality Assurance 
QC 
Quality Control 
RBC 
red blood cell 
RRM 
relapse-related mortality 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TBI 
total body irradiation 
TRM 
transplant-related mortality 
ULN 
upper limit of normal 
VZV 
Varicella zoster virus 
WBC 
white blood cell 

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WHO 
World Health Organization 
WHO-UMC 
World Health Organization Uppsala Monitoring Centre 
WNV 
West Nile virus 

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1 INTRODUCTION 
For many end stage patients with hematologic malignancies such as acute leukemias and 
myelodysplastic syndrome (MDS), a hematopoietic stem cell transplantation (HSCT) 
remains the only curative option. However, even though an allogeneic stem cell 
transplantation can provide a cure in contrast to most other treatments, it is not a first line 
treatment, because of complications related to the procedure.  
One of the major complications of allogeneic HSCT (both with matched sibling donors and 
unrelated matched donors) is the occurrence of acute graft versus host disease (GvHD), in 
which the T-cells from the donor react against the tissue of the patient. Without prophylactic 
use of immunosuppressants post transplantation the incidence of acute GvHD can approach 
100% (Goker et al. 2001) and even with prophylactic use of immunosuppressants 30-60% of 
patients will develop some level of acute GvHD (Abo-Zena and Horwitz 2002; Jagasia et al. 
2012; Ruggeri et al. 2006). 
GvHD is subdivided into acute GvHD and chronic GvHD (Glucksberg et al. 1974; Horwitz 
and Sullivan 2006; Jagasia et al. 2015; Przepiorka et al. 1995; Vogelsang 2001). Acute 
GvHD is responsible for significant morbidity and up to 20% of mortality in allogeneic stem 
cell recipients (from HLA-matched sibling and unrelated matched donors) (Martino et al. 
1999; Pasquini and Zhu 2015). 
In order to manage the risk of acute GvHD it is currently essential that a matched donor can 
be found. For patients who are eligible for an allogeneic HSCT and who do not have a human 
leukocyte antigen (HLA)-matched sibling, an allogeneic HSCT from an HLA-matched 
unrelated donor is an alternative option (Gratwohl et al. 2007; Ljungman et al. 2006). The 
use of a matched (related or unrelated) donor is considered standard of care for patients who 
are eligible for an HSCT. However, a major limitation of using matched donors is that for a 
significant number of patients a matched unrelated donor cannot be found in a timely manner 
and consequently many patients do not receive this treatment. If family members who are 
only partially HLA-matched to the recipient (haploidentical donors) could be used as stem 
cell donor, up to 95% of patients in urgent need for an HSCT could find a donor and receive 
this potentially life-saving treatment. Almost all patients have at least one partially HLA-
matched parent, sibling, or child, who is eligible as a donor. The immediate availability of 
this mismatched family member can have important treatment implications as a patient’s 
condition can deteriorate during a search period to look for a fully HLA-matched donor in 
the donor bank. 
The haploidentical transplant procedure has become feasible through use of methods to 
remove T-cells from the graft (T-cell depletion), in order to reduce the risk of (acute) GvHD, 
and subsequent administration of a megadose of CD34+ cells (Champlin et al. 2002; Tabilio 
et al. 2004). However, the downside of this approach is that patients remain severely immune 
compromised for a prolonged period of time, with a high risk of life-threatening infections 
resulting in a high treatment-related mortality (TRM) rate (Koh et al. 2007). Larger series 
have shown the outcome of these transplants to remain disappointing with 2-year leukemia 
survival ranging between 20-40% (Ciceri et al. 2007). One way to potentially reduce this 

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high TRM rate is to provide functional T-cells to the patient early after the stem cell 
transplantation through a donor lymphocyte infusion (DLI), which can lead to faster immune 
reconstitution and provide early protection against opportunistic infections. However, giving 
unmanipulated, mature T-cells early after the stem cell transplantation, especially if more 
than 1×104 cells/kg are infused, may lead to life-threatening acute GvHD (Aversa et al. 1998; 
Lewalle et al. 2003), making this approach impractical. 
Removal of alloreactive T-cells, which would cause acute GvHD, could make it possible to 
infuse a high dose of T-cells after the transplantation, without increasing the risk of GvHD. 
Kiadis Pharma Netherlands B.V. (hereafter Kiadis Pharma) is developing ATIR101 
(previously referred to as ATIR), a T-lymphocyte enriched leukocyte preparation depleted ex 
vivo of host alloreactive T-cells using photodynamic treatment (PDT). ATIR101 is 
manufactured through the ex vivo use of TH9402 and PDT (Theralux platform). Kiadis 
Pharma has demonstrated that TH9402 in vitro accumulates in human T-cells activated with 
allogeneic major histocompatibility complex (MHC)-mismatched cells and upon light 
activation selectively depletes these cells while anti-third party immune responses is 
preserved (Guimond et al. 2000). In addition, in a lethally irradiated murine model of 
mismatched allogeneic transplantation, ex vivo treatment of activated T-cells before their in 
vivo administration allowed 90% of the mice to survive more than 100 days. Moreover, the 
cells treated ex vivo with TH9402 and PDT, retained the ability to induce GvHD in third-
party mice and graft versus leukemia (GvL) function (Boumedine et al. 2004; Guimond et al. 
2002). Several investigators have confirmed the selective depletion of alloreactive cells by ex 
vivo treatment with TH9402 and PDT in HLA-mismatched stimulator-responder pairs 
(Mielke et al. 2008).  
A different approach for haploidentical donor transplants has been developed by 
investigators from Baltimore (Luznik et al. 2010). They use unmanipulated bone marrow 
grafts and administer a high dose of cyclophosphamide (50 mg/kg) on Day 3 and 4 after the 
HSCT, in order to eliminate reactive T-cells in the body. Additionally, these patients are 
given immunosuppressants for a prolonged period. Although this approach has shown to 
limit TRM and to make these transplants feasible, a high rate of relapse is observed, 
potentially due to the use of immunosuppressants (Brunstein et al. 2011). In addition, a 
relatively high rate of GvHD is still observed (Kanakry et al. 2014). 
Clinical Experience with ATIR101 
In a phase I/II study (CR-GVH-001), conducted at the Maisonneuve-Rosemont Hospital in 
Montreal, patients with high risk hematologic malignancies eligible for an allogeneic HSCT, 
but for whom a matched donor was not available, were treated with a haploidentical HSCT 
followed by a single infusion of ATIR101. ATIR101 was administrated 28-40 days following 
the transplantation of a CD34-selected stem cell graft, without adding immunosuppressive 
therapy after the HSCT, unless clinically indicated. After infusing a dose of 1×104 cells/kg to 
the first patient (L1), cohorts of 3 patients were exposed to increasing doses of ATIR101, 
starting at 5×104 cells/kg (L2) and escalating upwards to 5×106 cells/kg (L7). A total of 
19 patients have been infused with ATIR101 at different cell dose levels. No patient 
experienced grade III-IV acute GvHD, and no ATIR101-related serious adverse events were 

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reported. Based on this study the maximum tolerated dose of ATIR101 could not be 
determined, but there was a clear clinical difference between the lower and higher dose 
ranges. Within 2 years after the HSCT, TRM was observed in 6 patients, 4 in the lower dose 
cohorts (L1-L3; up to 1.3×105 cells/kg), 2 in the highest dose cohort (L7; 5×106 cells/kg) and 
none in the dose cohorts L4-L6 (3.2×105 - 2.0×106 cells/kg). Long-term follow-up (5 years) 
in the effective dose range between 3.2×105 and 2.0×106 cells/kg (L4-L6) showed that none 
of the 9 patients died due to TRM (3 out of 9 patients died to RRM) and 6 out of 9 patients 
survived for more than 5 years, which was an unexpectedly high survival rate, as only a few 
patients were in complete remission at the time of transplantation. This study shows that 
ATIR101 at an effective dose is safe and well-tolerated as an addition to a T-cell depleted 
haploidentical HSCT and reduces TRM. Based on the results of study CR-GVH-001, the 
optimal dose of ATIR101 for further development was considered to be 2×106 T-cells/kg.  
In an ongoing phase II multicenter study (CR-AIR-007), conducted in Europe and North 
America, 23 patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic 
leukemia (ALL), or myelodysplastic syndrome (MDS) are planned to be treated with a single 
infusion of 2×106 cells/kg ATIR101 following a haploidentical HSCT. At the interim 
analysis (conducted in September 2014), 10 patients had been treated with ATIR101 (2×106 
cells/kg) and had completed at least 6 months of follow-up after the HSCT. Three of the first 
10 patients had died at the cut-off, all due to TRM caused by an infection, with 2 patients 
dying within the first 6 months post HSCT, resulting in a TRM rate at 6 months post HSCT 
(primary endpoint) of 20% (2/10). All death cases were judged to be unrelated to ATIR101 
infusion. A delay in the occurrence of TRM and severe infections was seen compared to a 
similar set of 35 patients undergoing a T-cell depleted haploidentical HSCT without the 
addition of T-cells post HSCT (preliminary data from observational cohort study CR-AIR-
006). No ATIR101-related cases of acute GvHD grade III/IV were reported, showing the 
effective elimination of alloreactivity. In the patients who showed (mild) acute GvHD the 
onset of the disease was quite delayed (not before 131 days post HSCT). Among the first 10 
patients, six patients (60%) were free of severe infections (i.e. NCI grade 3-5) between 
ATIR101 infusion and 6 months post HSCT. No cases of relapse or disease progression were 
observed. T-cell reconstitution (i.e. ≥ 0.2×109/L) was observed about 6 months after the 
HSCT. These interim results support continuation of patient enrolment. 
Study Rationale 
The objective of the current study is to study the safety and efficacy of a repeat dose 
administration of ATIR101 (two doses of 2×106 viable T-cells/kg body weight) in patients 
with a hematologic malignancy who received a T-cell depleted haploidentical HSCT. In the 
previous clinical studies with ATIR101, a single dose of 2×106 cells/kg was found to be safe 
(no acute GvHD grade III/IV). In study CR-AIR-007 we observed that no patients died 
within the first 100 days post HSCT and that T-cell reconstitution was seen around 6 months 
after the HSCT. Before T-cell reconstitution was reached, two patients had died due to 
systemic viral infections. The infusion of a second dose of ATIR101 at 70-74 days after the 
HSCT might further reduce the time to T-cell reconstitution and thereby decrease the 
occurrence of severe infections and TRM, while it is not expected to jeopardize patient safety 
by causing acute GvHD grade III/IV. 

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Risk-benefit Assessment 
For many end stage patients with a hematologic malignancy, an HSCT remains the only 
curative option. The use of a matched (related or unrelated) donor from the donor registries is 
considered standard of care for patients who are eligible for an HSCT. However, a significant 
number of patients do not receive this potentially life-saving treatment, because a suitable 
matched related or unrelated donor cannot be found in a timely manner or cannot be found at 
all.  
This protocol offers patients in need of an HSCT, who lack a suitable HLA-matched sibling 
or unrelated donor, the opportunity to receive a potentially life-saving treatment by the use of 
mismatched relatives, who are only partially HLA-matched to the recipient, as stem cell 
donor (haploidentical donors), followed by the administration of donor lymphocytes, which 
have been selectively depleted of host alloreactive T-cells (ATIR101). It is expected that 
patients will benefit from ATIR101 by protecting them from life-threatening infections 
without increasing the risk of life-threatening GvHD. Moreover, the possibility that the anti-
malignancy effects of the T-cells have been preserved could provide another benefit to the 
patients. This potential graft versus leukemia effect could reduce the risk of relapse and 
thereby further increase the probability of long-term survival.  
In conclusion, the current study offers patients with a hematologic malignancy in (urgent) 
need of an HSCT, a reasonable chance to improve their survival probability. Therefore, 
participation in this study provides patients the prospect of direct benefit. 
The following potential adverse reactions of ATIR101 are listed in the Investigator's 
Brochure: 
• Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) related reactions. 
Because ATIR101 consists of donor T-lymphocytes, the causal relationship between 
CMV/EBV related adverse events and ATIR101 administration cannot be ruled out if the 
donor is positive for CMV/EBV at screening. In this study a mandatory regimen to 
prevent and treat CMV and EBV disease will be implemented (see Section 5.6.4). 
• Post Transplant Lymphoproliferative Disease (PTLD) 
Because ATIR101 contains donor T-lymphocytes, the causal relationship between PTLD 
and ATIR101 administration cannot be ruled out if the donor is positive for EBV at 
screening. 
• Infusion reactions. 
Potential adverse reactions after the infusion could include allergic reactions to the 
ingredients of ATIR101: immediate fever or chills, skin rash, bronchospasm, or 
anaphylactic shock, and delayed serum-sickness-like reactions.  
• Graft versus host disease. 
Due to the ATIR101 manufacturing process and the possibility that a small percentage of 
alloreactive T-cells could remain in ATIR101, a causal relationship between acute or 
chronic GvHD and ATIR101 administration cannot be ruled out completely. 
 

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2 STUDY OBJECTIVE 
The objective of the study is to study the safety and efficacy of a repeat dose administration 
of ATIR101 in patients with a hematologic malignancy who received a T-cell depleted 
haploidentical HSCT. 

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3 INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study CR-AIR-008 is an exploratory, open-label, multicenter study. After signing informed 
consent, patients will receive an HSCT from a related, haploidentical donor, followed by a 
first ATIR101 infusion at a dose of 2×106 viable T-cells/kg between 28 and 32 days after the 
HSCT. Patients will receive a second ATIR101 infusion at a dose of 2×106 viable T-cells/kg 
between 70 and 74 days after the HSCT.  
To evaluate safety of the second dose administration, the first 6 patients treated will be 
evaluated for the occurrence of dose-limiting toxicity (DLT), defined as acute GvHD grade 
III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in 
case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the 
remaining 9 patients will continue with two ATIR101 infusions of 2×106 viable T-cells/kg. If 
within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be 
adjusted to a dose of 1×106 viable T-cells/kg. If in one of the next 3 patients treated at this 
lower dose again DLT is observed, the second ATIR101 infusion will be halted and the 
remaining patients will be given only a single dose of ATIR101.  
All patients treated with ATIR101 will be followed up until 12 months after the HSCT. 
Assessments will be performed at weekly visits from the day of the first ATIR101 infusion 
(Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 
4 until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT. 
See Appendix 1 for a detailed schedule of assessments. 
3.2 
Rationale for Study Design 
In the phase I/II study CR-GVH-001 and the phase II study CR-AIR-007 single doses of 
ATIR101 up to 5×106 viable T-cells/kg have been infused without causing any acute GvHD 
grade III/IV. Therefore, two doses of 2×106 viable T-cells/kg are expected to be safe and well 
tolerated as well, not exceeding the maximum dose exposure in prior studies. However, to 
ensure patient safety, a safety evaluation will be conducted on the first six patients at 120 
days post HSCT (see Sections 3.1 and 5.3).  
3.3 
Study Duration 
ATIR101 will be administered as two intravenous infusions at 28-32 and 70-74 days after the 
HSCT, respectively. Patients treated with ATIR101 will be followed up until 12 months after 
the HSCT. The end of the study is defined as the date at which the last data point from the 
last patient is received.  
The study is anticipated to be conducted between October 2015 and June 2017. 

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4 STUDY POPULATION SELECTION 
4.1 
Study Population 
In total, 15 patients with a hematologic malignancy who are eligible for a haploidentical 
HSCT will be treated with two doses of ATIR101 (unless the second dose is halted for safety 
reasons).  
4.2 
Patient Inclusion Criteria 
Each patient must meet the following criteria to be enrolled in this study. 
• Any of the following hematologic malignancies: 
- 
Acute myeloid leukemia (AML) in first remission with high-risk features or in second 
or higher remission 
- 
Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in 
second or higher remission 
- 
Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher 
IPSS-R risk group 
• Karnofsky performance status ≥ 70% 
• Eligible for haploidentical stem cell transplantation according to the investigator 
• Male or female, age ≥ 18 years and ≤ 65 years 
 
4.3 
Patient Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study. 
• Availability of a fully matched related or unrelated donor following a donor search 
• Diffusing capacity for carbon monoxide (DLCO) < 50% predicted 
• Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA) 
• AST > 2.5 x ULN (CTCAE grade 2) 
• Bilirubin > 1.5 x ULN (CTCAE grade 2) 
• Creatinine clearance < 50 mL/min (calculated or measured) 
• Positive HIV test 
• Positive pregnancy test (women of childbearing age only) 
• Prior allogeneic HSCT 
• Estimated probability of surviving less than 3 months 
• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide) 
• Known presence of HLA antibodies against the non-shared donor haplotype 
• Any other condition which, in the opinion of the investigator, makes the patient ineligible 
for the study 
 

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4.4 
Donor Inclusion Criteria 
Each donor must meet the following criteria to be enrolled in this study. 
• Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of 
the unshared haplotype 
• Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for 
donors under the age of 18 will be followed) 
• Eligible for donations of human blood and blood components according to local 
requirements and regulations 
• Eligible for donation according to the transplantation center 
 
4.5 
Donor Exclusion Criteria 
Donors who meet any of the following criteria will be excluded from the study. 
• Positive pregnancy test or nursing (women of childbearing age only) 
• Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV-1 (if 
tested), HTLV-2 (if tested), or WNV (if tested) 
 

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5 STUDY TREATMENT 
5.1 
Description of Treatment 
5.1.1 
Hematopoietic Stem Cell Transplantation 
The collection and preparation of the donor stem cell graft is performed according to 
institutional procedures at the study center. The study centers will mobilize PBSCs from the 
donor with granulocyte colony-stimulating factor (G-CSF) administered subcutaneously at a 
dose of approx. 8 µg/kg twice daily for approx. 4 to 7 days. The PBSCs will be collected by 
apheresis. According to the Perugia protocol for haploidentical transplants, the CD34-
selected stem cell graft is targeted to contain at least 5×106 CD34+ cells/kg but if possible 
8-11×106 CD34+ cells/kg with a maximum of 3×104 CD3+ cells/kg as assessed by flow 
cytometry (Champlin et al. 2002; Tabilio et al. 2004). To ensure a consistently highly 
purified stem cell graft, clinical sites will use the CliniMACS® CD34 isolation system (from 
Miltenyi Biotec) as part of their institutional procedures for preparing the stem cell graft. 
In order to prepare the patient for the HSCT one of the following myeloablative conditioning 
regimens is recommended. Deviations from these recommended conditioning regimens are to 
be discussed between the coordinating investigator, Kiadis Pharma, and the investigator of 
the respective site. 
• Fractionated total body irradiation (TBI); 200 cGy twice daily for 3 days on Day -10 to -8 
(1200 cGy in 6 fractions) 
TBI regimen 
• Fludarabine; 30 mg/m2 intravenously (IV) once daily for 5 days on Day -7 to -3 
• Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 
• Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on 
Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients 
will receive methylprednisolone 2 mg/kg/day IV. 
 
• Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 
Non-TBI regimen 
• Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 
• Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 
• ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a 
continuous IV infusion for 8 hours. During the course of ATG, patients will receive 
methylprednisolone 2 mg/kg/day IV. 
 
5.1.2 
Investigational Medicinal Product (ATIR101) 
For manufacturing of ATIR101, donor and patient peripheral blood mononuclear cells 
(PBMCs) as well as donor plasma are collected by apheresis according to the procedure 
described in the Product Handling & Shipping Manual as well as Kiadis Pharma-defined 

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specifications for cell content. For the patient this apheresis is done in advance of the 
conditioning regimen for the HSCT and for the donor this additional apheresis is done in 
general 0.5-3 weeks before the apheresis for the stem cell graft. Donation, collection and 
testing of human tissues and cells will be done in compliance with relevant local regulations. 
The apheresis materials will be prepared for temperature-controlled shipment and shipped to 
the manufacturing facility according to the procedure that is described in the Product 
Handling & Shipping Manual. ATIR101 will be manufactured at two manufacturing 
facilities, under supervision of Kiadis Pharma: the Centre d’Excellence en Thérapie 
Cellulaire, Hôpital Maisonneuve-Rosemont (Montréal, Canada) and the Deutsches Rotes 
Kreuz-Blutspendedienst Baden-Württemberg-Hessen (Frankfurt am Main, Germany). Cell 
processing at the manufacturing facility will start as soon as possible but within 24 hours 
after the end of the apheresis.  
The selective depletion of host alloreactive T-cells in ATIR101 is shown schematically 
below (Figure 1). During processing patient and donor cells are co-cultured in a mixed 
lymphocyte reaction (MLR) to stimulate activation of host alloreactive T-cells (the patient 
cells are gamma irradiated prior to the MLR). In the MLR, donor lymphocytes are activated 
against the major discordant MHC antigens of the irradiated patient’s cells. Subsequent ex 
vivo PDT, using the photosensitizing compound TH9402, depletes the host alloreactive 
T-cells resulting in the cellular product ATIR101. Those cells that are activated accumulate 
more light-sensitive TH9402 than non-activated cells and are consequently more susceptible 
to the effect of PDT treatment. The T-lymphocyte enriched leukocyte preparation depleted ex 
vivo of host alloreactive T-cells (ATIR101) is cryopreserved until infusion into the patient 
following the HSCT. The whole manufacturing process takes 5 days and additional quality 
control tests for product release take 14 days. 
For each patient batch, two 20-mL units (bags) of ATIR101 will be prepared, containing 
2×106 viable T-cells/kg. A third unit (bag) will contain the remaining ATIR101 cells 
(10-20 mL equivalent with a dose of 1-2×106 viable T-cells/kg) and can be used as a rescue 
dose when required. The units are frozen and stored until release to the sites. 
Each batch of ATIR101, manufactured for the individual patient, will be tested on key 
quality attributes, of which depletion of alloreactivity is crucial. After formal release, each 
frozen ATIR101 unit will be shipped separately to the clinical site just before ATIR101 
infusion is required.  
Retain- and research samples of ATIR101, the starting materials, and any intermediates are 
taken and stored. The research samples can be used for performing tests to further optimize 
the ATIR101 manufacturing process and better understand the mechanism of action of 
ATIR101. None of the samples will be used for genetic research purposes. 

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Figure 1 
Schematic overview of the ATIR101 procedure 
 
5.2 
Treatments Administered 
ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host 
alloreactive T-cells using PDT with the photosensitizing reagent TH9402.  
ATIR101 is presented as a “solution for infusion”. The cell suspension contains 2.5-13×106 
viable T-cells/mL (for a patient weight range of 25-130 kg), 10% DMSO, and 30% donor 
plasma in saline 0.9%. The total volume of a unit is 20 mL (dose 2×106 viable T-cells/kg). 
ATIR101 will be infused intravenously at a dose of 2×106 viable T-cells/kg body weight 
between 28 and 32 days after the HSCT (or later if required by the patient's medical 
condition). If not halted for safety reasons, patients will receive a second ATIR101 infusion 
between 70 and 74 days after the HSCT but at least 42 days after the first ATIR101 infusion 
(or later if required by the patient's medical condition). The second ATIR101 infusion will 
consist of a dose of 2×106 viable T-cells/kg (or an adjusted dose of 1×106 viable T-cells/kg 
when required). 

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ATIR101 will not be infused if at the time of the planned infusion: 
• The patient is suffering from active GvHD (any grade), and/or 
• The patient is receiving steroid-based immunosuppressive therapy (excluding topical 
steroids). 
 
In the event the patient fails to demonstrate hematologic engraftment (neutrophil count 
≥ 0.5×109/L for 2 consecutive days and platelets ≥ 20×109/L for 3 consecutive days, without 
transfusion) bone marrow aspirate and biopsy will be performed and infusion of ATIR101 
will be decided on a case by case basis after discussion between the coordinating 
investigator, Kiadis Pharma, and the investigator of the respective site. 
ATIR101 will be shipped frozen to the clinical sites in a dry shipper saturated with liquid 
nitrogen guaranteeing a temperature < -135 °C for at least 7 days; ATIR101 will remain 
stored in the dry shipper until infusion. The frozen product should be thawed in approx. 
2 minutes at the bedside and the entire unit should be infused intravenously immediately (i.e. 
when last ice crystals are dissolved). In general, the time from the moment ATIR101 has 
been thawed (i.e. temperature 0 °C without any ice crystals) until infusion of the entire unit 
(including rinsing the infusion bag with saline) should not take more than 10 minutes. 
Detailed instructions on the thawing and infusion process are provided in the Product 
Handling & Shipping Manual. Patients will be carefully monitored up to 4 hours after the 
infusion for any infusion reactions.  
5.3 
Selection and Timing of Dose for Each Patient 
To evaluate safety of the second dose administration, the first 6 patients treated will be 
evaluated for the occurrence of dose-limiting toxicity (DLT), defined as acute GvHD grade 
III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in 
case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the 
remaining 9 patients will continue with two ATIR101 infusions of 2×106 viable T-cells/kg. If 
within the first 6 patients at least two patients show DLT, the second ATIR101 infusion will 
be adjusted to a dose of 1×106 viable T-cells/kg. If in one of the next 3 patients treated at this 
lower dose again DLT is observed, the second ATIR101 infusion will be halted and the 
remaining patients will be given only a single dose of ATIR101.  
The actual dose of ATIR101 (number of viable T-cells) will be based on the patient’s body 
weight at screening. When the patient’s body weight at the time of ATIR101 administration 
differs from the patient’s body weight at screening, the dose should not
Intravenous infusion of the first ATIR101 dose will be scheduled between 28 and 32 days 
after the HSCT (or later if required by the patient's medical condition). The second ATIR101 
dose will be scheduled between 70-74 days after the HSCT but at least 42 days after the first 
ATIR101 infusion (or later if required by the patient's medical condition). 
 be adjusted. 
If beyond 120 days after the HSCT, according to the treating physician, a donor lymphocyte 
infusion is indicated (e.g., due to impending relapse or graft failure), a rescue dose of 
ATIR101 might be considered, if available. The investigator can request Kiadis Pharma for 

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shipment of an ATIR101 unit containing a rescue dose. This request should be supported by 
a clinical rationale for the infusion of a rescue dose.  
5.4 
Method of Assigning Patients to Treatment Groups 
In this study all eligible patients will receive two units of 2×106 viable T-cells/kg ATIR101, 
unless the occurrence of DLT requires a decrease or halt of the second dose (see Section 5.3). 
5.5 
Blinding 
In this open-label study no blinding will be applied. 
5.6 
Concomitant Therapy 
All medications used during the study, except for ATIR101, will be considered concomitant. 
The following concomitant medications should be recorded in the electronic case report form 
(eCRF): 
• Medication for the treatment of GvHD 
• Medication for the treatment of infections, including prophylactic or preemptive use of 
anti-infective medication 
• Medication for the treatment of disease relapse 
• Medication for the treatment of other reported adverse events 
• Additional hematopoietic stem cell grafts 
• Additional lymphocyte infusions 
• Hematopoietic growth factors 
• Vaccinations 
 
5.6.1 
Immunosuppressives 
Detailed recommendations on the treatment of graft versus host disease are provided in a 
separate guidance document. 
Post-transplantation immunosuppressive therapy (e.g. corticosteroids) in the absence of 
GvHD should be avoided unless medically indicated. The use of immunosuppressives shortly 
before infusion of ATIR101 or thereafter will inhibit the effects of ATIR101.  
GvHD is treated based on institutional standards. Limited GvHD of the skin should be 
treated locally only (steroid cream). Advanced stages and confirmed gut or liver GvHD 
require treatment according to institutional policy (e.g. IV steroids 1 mg/kg prednisolone).  
5.6.2 
Hematopoietic Growth Factors 
Usually engraftment is rapid without G-CSF treatment. G-CSF has shown to reduce T-cell 
reactivity (Franzke et al. 2003). Therefore, post-transplantation G-CSF treatment should be 

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avoided unless medically indicated. The use of G-CSF will be at the discretion of the 
investigator. 
5.6.3 
Donor Lymphocyte Infusions (DLIs) 
It is not allowed to treat patients with an unmanipulated DLI
5.3
. If a DLI is indicated beyond 
120 days post HSCT (e.g., due to impending relapse or graft failure) a rescue dose of 
ATIR101 might be considered, if available (see also Section 
). The investigator can 
request Kiadis Pharma for shipment of an ATIR101 unit containing a rescue dose. This 
request should be supported by a clinical rationale for the infusion of a rescue dose. 
5.6.4 
Anti-viral Drugs 
Detailed recommendations on the prophylactic and preemptive treatment of viral infections 
are provided in a separate guidance document. 
5.6.4.1 
Cytomegalovirus (CMV) 
• Mandatory CMV prophylaxis including ganciclovir and foscarnet. The following dosing 
schedule is recommended (Day 0 is the day of the HSCT): 
In case of CMV positive recipient and/or donor:  
• From Day -9 through Day -2: ganciclovir 5 mg/kg IV q12h. 
• From Day 4 through Day 20: foscarnet 90 mg/kg IV q24h. 
• From Day 21 until Day 100: valganciclovir 900 mg PO daily 5 days a week, or 
ganciclovir 5 mg/kg IV q24h 5 days a week. 
• Dosage is to be adjusted depending on renal function.  
 
• Weekly CMV monitoring by quantitative PCR from HSCT until Week 16 after the 
HSCT, monthly until Month 6 after the HSCT, and every 3 months until Month 12 after 
the HSCT. More frequent CMV monitoring is recommended depending on the patient's 
risk and the investigator's judgment. 
All patients 
• If quantified viral DNA levels exceed the institutional threshold for treatment of CMV 
(as established for each study center before participation in the study), patients should be 
treated with ganciclovir (recommended dose 5 mg/kg IV q12h) or valganciclovir 
(recommended dose 900 mg PO BID). 
 
5.6.4.2 
Epstein-Barr Virus (EBV) 
• If donor or patient is EBV positive before transplantation or as indicated, EBV will be 
monitored weekly until Week 16 after the HSCT, monthly until Month 6 after the HSCT, 
In case of EBV positive recipient and/or donor:  

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and every 3 months until Month 12 after the HSCT. More frequent EBV monitoring is 
recommended depending on the patient's risk and the investigator's judgment. 
• If quantified viral DNA levels exceed the institutional threshold for treatment of EBV (as 
established for each study center before participation in the study), patients should be 
treated with rituximab.  
The following schedule is recommended: 
1. Immediately after the rise in EBV DNA is detected, rituximab (anti-CD20) 
375 mg/m2 IV is started once weekly, until PCR for EBV becomes negative.  
2. If PTLD is suspected on the basis of clinical symptoms, CT scans of thorax, abdomen 
and pelvis, as well as bone marrow aspiration and biopsy, and -when possible- lymph 
node biopsy should be conducted. If results of the CT scan, bone marrow 
examinations, and lymph nodes demonstrate PTLD, rituximab is repeated weekly for 
at least 2 weeks. 
• It is also recommended to start rituximab if a patient who was EBV positive in the past, 
demonstrates enlarged lymph nodes, even if PCR for EBV is low or negative. 
 
5.6.4.3 
Herpes Simplex Virus (HSV) 
If during the study the investigator assesses the patient to be HSV positive but CMV 
negative, prophylactic treatment is recommended for at least 1 year and continued 
subsequently until the CD4+ lymphocyte count is above 0.2×109/L. 
5.6.4.4 
Varicella Zoster Virus (VZV) 
If during the study the investigator assesses the patient to be VZV positive, prophylactic 
treatment is recommended for at least 1 year and continued subsequently until the CD4+ 
lymphocyte count is above 0.2×109/L. If the patient is VZV positive and CMV positive, 
prophylactic treatment is recommended for at least 1 year and until the CD4+ lymphocyte 
count is above 0.2×109/L (even if the patient receives ganciclovir or valganciclovir for CMV 
treatment). 
5.6.5 
Anti-bacterial, Anti-parasitic, and Anti-fungal Drugs 
Detailed recommendations on the prophylactic treatment of bacterial, parasitic, and fungal 
infections are provided in a separate guidance document. 
Prophylactic treatment against bacterial, parasitic and fungal infections prior to or post-
transplantation according to institutional practices is recommended. 
5.7 
Treatment Compliance 
Drug accountability of ATIR101 will be documented at the study centers. 
5.8 
Packaging and Labeling 
ATIR101 will be packed in infusion bags as units of 20 mL (dose 2×106 viable T-cells/kg). 
Labeling will be done in accordance with applicable international guidelines. 

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5.9 
Storage and Accountability 
ATIR101 must be stored in liquid nitrogen (vapor phase). Storage of ATIR101 at the site is 
described in detail in the Product Handling & Shipping Manual. 
In accordance with international guidelines, both Kiadis Pharma and the manufacturing 
facility will maintain records of all investigational products dispensed worldwide. After the 
completion of the study, the manufacturing facility will take a full account of the product and 
provide it to Kiadis Pharma. All waste materials that have been used for the preparation 
and/or administration of ATIR101 at the manufacturing facility and at the study site will be 
destroyed according to local regulations. 
In this study traceability is defined as the ability to locate and identify each individual unit of 
blood cells/plasma during any step from apheresis, through processing, testing and storage, to 
distribution of ATIR101 to the patient or disposal and vice versa. This also implies the ability 
to identify the donor, the ability to identify the patient at the study site and the ability to 
locate and identify all relevant data relating to products and materials coming into contact 
with those blood cells/plasma. 
Traceability 
Traceability of patients and donors is ensured by documenting the identity of patients and 
donors including their donor/patient number at the study site. Both patient and donor 
identities are protected and are only identified by code numbers that can be linked at the 
study site to their full identity. 
Traceability of blood cells/plasma from apheresis until distribution of ATIR101 is ensured by 
the procedures of the manufacturing facility. Traceability of ATIR101 at the study site is 
ensured by maintaining an accountability log. 
In accordance with international guidelines, Kiadis Pharma will maintain records of the 
origin of all cellular materials (donor lymphocytes) for a period of 30 years.  

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6 STUDY PROCEDURES 
6.1 
Informed Consent 
Prior to participation in the study, each patient and his/her donor will sign the informed 
consent form. More details on the informed consent are given in Section 10.3. 
6.2 
Patient Characteristics and Eligibility 
Date of birth and gender of the patient will be recorded. 
Demographics 
WHO classification of hematologic malignancy (Vardiman et al. 2009), cytogenetic and 
molecular abnormalities, date of first diagnosis, and presence of minimal residual disease 
will be recorded. 
Hematologic malignancy 
The EBMT risk score will be assessed according to Gratwohl (Gratwohl 2012; Michallet et 
al. 2010). See Appendix 2 for details. 
All prior treatments for the hematologic malignancy will be recorded, including treatments 
that led to previous remissions if applicable. 
All existing medical conditions at the time of screening and other relevant medical history 
including information on previous malignancies will be recorded. Comorbidity will be 
assessed according to the items of the hematopoietic cell transplantation-specific comorbidity 
index (HCT-CI) (Sorror et al. 2005) (see 
Medical history 
Appendix 3).  
Performance status will be assessed as a percentage (0-100%) according to the Karnofsky 
Performance Status (KPS) scale (Schag et al. 1984) (see 
Performance status 
Appendix 4). 
At least the following body systems will be examined: skin, ears/nose/throat (ENT), 
respiratory, cardiovascular, abdomen (including liver and spleen), and lymph nodes. All 
abnormal findings will be recorded. 
Physical examination 
A high resolution CT scan of the thorax will be used to assess the presence of any 
generalized lung disease. This assessment may have been done within 6 weeks before signing 
informed consent. 
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An echocardiogram or MUGA scan will be used to assess the patient's cardiac function. This 
assessment may have been done within 6 weeks before signing informed consent. 
Echocardiogram or MUGA scan 
A pulmonary function test will be used to assess the functional status of the lungs. This 
assessment may have been done within 6 weeks before signing informed consent. 
Pulmonary function test 
To assess renal function creatinine clearance will be either calculated or measured: 
Creatinine clearance 
• Calculation by using the Cockcroft-Gault formula (Cockcroft and Gault 1976) 
 
𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 [mL/min] =
(140 −𝐴𝑔𝑒) × 𝑊𝑒𝑖𝑔ℎ𝑡 [𝑘𝑔] × 0.85[𝑖𝑓 𝑓𝑒𝑚𝑎𝑙𝑒]
72 × 𝑆𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [mg/dL]
 
• Measurement by collecting 24-hour urine 
 
Creatinine clearance [mL/min] = 𝑈𝑟𝑖𝑛𝑒 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [𝑚𝑔/𝑑𝐿] × 𝑈𝑟𝑖𝑛𝑒 𝑓𝑙𝑜𝑤 [𝑚𝐿/𝑚𝑖𝑛]
𝑆𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [mg/dL]
  
 
A pregnancy test will be performed in females unless the patient is diagnosed as 
postmenopausal or if surgically sterilized. 
Pregnancy test 
At screening, the patient’s blood will be tested for the presence of the following viruses (and 
other micro-organisms) in accordance with local regulatory requirements and regulations : 
EBV, CMV, HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HLTV-I (not in Europe), 
HLTV-II (not in Europe), and WNV (North America only; in Canada depending on area at 
risk and season).  
Viral testing 
6.3 
Donor Characteristics and Eligibility 
Date of birth and gender of the donor will be recorded as well as the family relation between 
donor and patient. 
Demographics 
Mismatches at the HLA-A, -B and/or -DR loci (and if available at the HLA-C and –DQ loci) 
of the unshared haplotype will be assessed. 
HLA compatibility 

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At screening, the donor's blood will be tested for the presence of the following viruses (and 
other micro-organisms) in accordance with local regulatory requirements and regulations for 
donations of human blood and blood components: EBV, CMV, HIV-1, HIV-2, HBV, HCV, 
Treponema pallidum, HLTV-I (not in Europe), HLTV-II (not in Europe), and WNV (North 
America only; in Canada depending on area at risk and season).  
Viral testing 
A pregnancy test will be performed in females unless the donor is diagnosed as 
postmenopausal or if surgically sterilized. 
Pregnancy test 
6.4 
Vital Signs 
The following vital sign parameters will be measured: respiration rate or oxygen saturation, 
pulse rate, temperature, weight, and supine blood pressure after 5 minutes of rest.  
In addition, following ATIR101 infusion, pulse rate and supine blood pressure will be 
assessed after 15 minutes, 1, 2, 3, and 4 hours. Continuous oxygen monitoring will be done if 
the patient has respiratory problems. 
6.5 
Safety Laboratory Tests 
Subjects will be in a seated or supine position during blood collection. Safety laboratory tests 
will include the following:  
Table 1  
List of safety laboratory tests 
- 
Hematocrit  
Hematology: 
- 
Hemoglobin  
- 
Mean corpuscular volume (MCV) 
- 
Platelet count 
- 
Red blood cell (RBC) count  
- 
White blood cell (WBC) count 
- 
Lymphocytes 
- 
Monocytes 
- 
Basophils 
- 
Eosinophils 
- 
Absolute neutrophil count (ANC) 
 
 
- 
Bilirubin 
Urinalysis:  
- 
Albumin 
Blood Chemistry: 
- 
Alkaline phosphatase (AP) 
- 
Alanine aminotransferase (ALT) 
- 
Aspartate aminotransferase (AST) 
- 
Calcium (Ca) 
- 
Chloride (Cl) 
- 
Creatinine 
- 
Glucose 
- 
Lactate dehydrogenase (LDH) 
- 
Magnesium (Mg) 
- 
Phosphorus (P) 
- 
Potassium (K) 
- 
Sodium (Na) 
- 
Total bilirubin 
- 
Total protein 
- 
Urea 

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- 
Glucose 
- 
Ketones 
- 
Nitrite  
- 
Blood 
- 
pH 
- 
Protein 
- 
Specific gravity 
- 
Leukocytes 
 
 
 
Patients will be monitored for CMV and EBV using local quantitative polymerase chain 
reaction (PCR) assays (see also Section 
CMV/EBV monitoring (PCR) 
5.6.4). 
Weekly CMV monitoring by quantitative PCR until Week 16 after the HSCT, monthly until 
Month 6, and every 3 months until Month 12. More frequent monitoring for CMV is 
recommended depending on the patient's CMV status at baseline and the investigator's 
judgment. 
If donor or patient is EBV positive before transplantation or as indicated, EBV will be 
monitored weekly until Week 16 after the HSCT, monthly until Month 6, and every 3 months 
until Month 12. More frequent monitoring for EBV is recommended depending on the 
patient's EBV status at baseline and the investigator's judgment. 
Engraftment is defined as neutrophil count ≥ 0.5×109/L for 2 consecutive days and platelets 
≥ 20×109/L for 3 consecutive days, without transfusion. The first days of occurrence of these 
two criteria will be recorded. 
Engraftment 
Primary graft failure is defined as lack of initial engraftment of donor cells. The patient never 
recovers from neutropenia (neutrophil count < 0.5×109/L), resulting in pancytopenia and an 
urgent need for re-transplantation. Secondary graft failure is defined as loss of donor cells 
after initial engraftment. In this case autologous recovery is common; however, marrow 
aplasia and pancytopenia may also develop. 
A blood sample for assessment of chimerism will be collected on the days of the ATIR101 
infusions, prior to the infusion of ATIR101. Chimerism will be assessed in peripheral blood 
lymphocytes and polynuclear cells (neutrophils) by PCR amplification. 
Chimerism 

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6.6 
Efficacy and Safety Assessments  
6.6.1 
Immune Reconstitution 
Immunophenotyping on peripheral blood samples by means of flow cytometry assessment of 
immune subsets should be done if the absolute lymphocyte count is higher than 0.1×109/L.  
Immunophenotyping 
Immunophenotyping assessments are planned at screening, just before the ATIR101 
infusions (Week 4 and Week 10), and at 5, 7, 9, 11, 12, 13, 14, 15, and 16 weeks after the 
HSCT, as well as at 5, 6, 9, and 12 months after the HSCT. 
The following cell markers / cell marker combinations are to be measured: 
• CD3+ identifying T-cells 
• CD3+ CD8+ identifying cytotoxic T-cells 
• CD3+ CD4+ identifying helper T-cells 
• CD3- CD56+ identifying natural killer (NK)-cells 
• CD19+ identifying B-cells 
 
All measurements must be reported in absolute numbers of circulating lymphocytes (×109/L) 
instead of percentages. 
The production of antibodies will be assessed by measuring the immunoglobulin levels of 
IgG, IgA, and IgM in peripheral blood. 
Immunoglobulins 
Immunoglobulin assessments are planned at screening, just before the ATIR101 infusions 
(Week 4 and Week 9), at 11, 13, and 16 weeks after the HSCT, as well as at 5, 6, 9, and 
12 months after the HSCT. 
Serum and peripheral blood will be collected for additional assessments of T-cell, B-cell and 
NK-cell reconstitution: 
Additional assessments 
• Serum samples for measuring cytokine levels and/or immunoglobulins against specific 
antigens (e.g. vaccine response), prepared from 8-10 mL whole blood, will be collected at 
screening, at HSCT, just before the ATIR101 infusions (Week 4 and Week 10), at 5, 7, 9, 
11, 12, 13, 14, 15, and 16 weeks after the HSCT, as well as at 5, 6, 9, and 12 months after 
the HSCT.  

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• Peripheral blood samples for measuring pathogen-specific T-cells will be collected at 
6 and 12 weeks after the HSCT, as well as 6 and 12 months after the HSCT and when a 
clinically relevant viral reactivation or infection is diagnosed. The required volume of 
peripheral blood depends on the absolute CD3 count: 
 
CD3 count (× 109/L): 
Required volume (mL): 
≤ 0.2 
50 
> 0.2 and ≤ 0.4 
35 
> 0.4 
20 
 
6.6.2 
Infection Assessment 
In this study an infection is defined as a clinically apparent infectious disease with symptoms 
or detectable viral reactivation. Details of all infections will be recorded on the Infection AE 
page of the eCRF, including start date, stop date, NCI CTCAE severity grade (see Section 
6.7), outcome, action taken. Whenever an infectious episode is suspected, appropriate 
diagnostic measures need to be taken, including blood cultures to allow assessment of the 
specific pathogen causing the infection. 
6.6.3 
Disease Assessment 
The status of the hematologic disease will be assessed regularly. Details of relapse or disease 
progression will be recorded on the Relapse/Disease Progression AE page of the eCRF (see 
Section 6.7). In case of suspected relapse chimerism will be assessed to support the 
diagnosis. In addition, a bone marrow aspirate and/or biopsy must be performed at fixed 
visits unless relapse has already been confirmed (Screening, Month 6 after HSCT, Month 12 
after HSCT) and in case of suspected relapse. If a bone marrow aspirate and/or biopsy was 
already performed within 6 weeks prior to a scheduled visit, the assessment does not need to 
be repeated. 
6.6.4 
Graft versus Host Disease Assessment 
In this study GvHD must be classified into acute and chronic GvHD according to its clinical 
manifestations (Filipovich et al. 2005). Acute GvHD will be graded according to standard 
criteria (Przepiorka et al. 1995), which is also done for the severity of chronic GvHD 
(Filipovich et al. 2005) (see details in Appendix 5). Whenever deemed feasible, tissue 
biopsies will be obtained to confirm the GvHD diagnosis and to assess its severity. If not 
available yet, unscheduled hematology and blood chemistry laboratory tests (see Table 1) 
must be done to support the diagnosis of GvHD. Details of all GvHD events will be recorded 
on the GvHD AE page of the eCRF. 
All GvHD cases will be subject to independent adjudication. If present, histological data are 
to be put at the adjudicator’s disposal. 

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6.6.5 
Mortality 
If a patient dies, the following information must be recorded in the eCRF: 
• Date of death 
• Cause of death (specification) 
• Investigator classification of cause of death into: 
• Disease relapse 
• Disease progression 
• Transplant-related mortality (TRM) defined as death due to causes other than disease 
relapse or progression, or other known causes which are unrelated to the 
transplantation procedure (e.g. accident, suicide) 
• Other known cause unrelated to the transplantation procedure or underlying disease 
(e.g. accident, suicide) 
 
All death cases will be subject to independent adjudication (see Section 10.8). 
6.7 
Adverse Events 
A pre-treatment adverse event (AE) is defined as any untoward medical occurrence in a 
clinical investigation patient who has participated in the pre-treatment period of the study but 
prior to administration of the investigational product; it does not necessarily have to have a 
causal relationship with study participation. 
Definition 
A treatment-emergent adverse event (AE) is defined as any untoward medical occurrence in 
a clinical investigation patient administered an investigational product or procedure and 
which does not necessarily have to have a causal relationship with study participation. 
A treatment-emergent AE can therefore be any unfavourable and unintended sign (including 
an abnormal laboratory finding, for example), symptom, or disease temporally associated 
with the use of a medicinal product or procedure, whether or not considered related to the 
medicinal product or procedure. 
Within this study, infections including all detectable viral reactivations (see Section 
Reporting of adverse events in patients 
6.6.2), 
relapse/disease progression (see Section 6.6.3), and GvHD (see Section 6.6.4) will be 
recorded separately, apart from the other AEs. While infections (including viral activations), 
relapse/disease progression and GvHD will be reported throughout the study, other AEs will 
only be reported until 16 weeks after the HSCT. AEs occurring before the first ATIR101 
infusion that are related to the conditioning regimen or the HSCT and are listed in Appendix 
6 do not need to be reported in the eCRF. However, all serious AEs
6.8
 during the study (see 
Section 
) must be reported in the eCRF. 

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Each event should be recorded as a single diagnosis. Accompanying signs (including 
abnormal laboratory values and ECG findings) or symptoms should not
Pre-existing conditions (present at the time of signing the informed consent) are considered 
concurrent medical conditions and should 
 be recorded as 
additional AEs. However, if the diagnosis is unknown or uncertain, signs and symptoms must 
be recorded. 
not
AEs will be evaluated using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE), version 4.0 (June 2010). All AEs, whether spontaneously reported by the patient, 
discovered during general questioning by the investigator, or detected through physical 
examination, laboratory test or other means will be recorded on the AE page of the eCRF. 
 be recorded as AEs but as medical history. 
However, if the patient experiences a worsening or complication of such a concurrent 
condition, the worsening or complication should be recorded. Investigators should ensure 
that the event term recorded captures the change in the condition (e.g., “worsening of…”). 
Each AE is to be evaluated for duration (start and end dates), severity grade and causal 
relationship with the study medication (certain, probable, possible, unlikely/unrelated). In 
addition, the actions taken for the AE will also be documented on the eCRF.  
All AEs that occur from signing the informed consent of the donor until collection of the 
stem cells must be recorded on the AE page of the donor eCRF, except for the AEs that are 
caused by the administration of G-CSF, which should not be reported. 
Reporting adverse events in donors 
The severity grade of an AE provides a qualitative assessment of the extent or intensity of an 
adverse event, as determined by the investigator or as reported by the patient. The severity 
grade does not reflect the clinical seriousness of the event, only the degree or extent of the 
affliction or occurrence (e.g. severe nausea, mild seizure).  
Severity 
The severity grade should be recorded in the eCRF according to the grading below. Severity 
grade for AEs will be based on the NCI CTCAE, version 4.0 (June 2010).*
1 = Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
  
2 = Grade 2:  Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living. 
3 = Grade 3:  Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self care 
activities of daily living. 
 
*  
Available on: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf 

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4 = Grade 4: Life-threatening consequences; urgent intervention indicated. 
5 = Grade 5: Death related to adverse event 
All AEs will be examined to determine any relationship to ATIR101 using the WHO-UMC 
system for standardized case causality assessment. The assessment criteria are listed below: 
Causal relationship 
Certain: 
• An event or laboratory test abnormality, with plausible relationship to 
administration of the investigational product. 
• The event cannot be explained by the disease or other drugs. 
• Response to withdrawal is plausible (pharmacologically, pathologically). 
• Event definitive pharmacological or phenomenological (i.e. an objective and 
specific medical disorder or a recognized pharmacological phenomenon). 
• Re-challenge satisfactory, if needed. 
 
Probable: 
• An event or laboratory test abnormality, with reasonable time relationship to 
administration of the investigational product. 
• Unlikely to be attributed to the disease or other drugs. 
• Response to withdrawal clinically reasonable. 
• Re-challenge not required. 
 
Possible: 
• An event or laboratory test abnormality, with reasonable time relationship to 
administration of the investigational product. 
• Could also be explained by the disease or other drugs. 
• Information on drug withdrawal may be lacking or unclear. 
 
Unrelated/Unlikely: 
• Event or laboratory test abnormality, with a time to administration of the 
investigational product that makes a relationship improbable (but not impossible). 
• Disease or other drugs provide plausible explanations. 
 
The actions taken in response to an adverse event are described on a numerical scale, from 0 
to 3 that cover the various possibilities. The actions taken, as presented in the eCRF, are 
provided below. One or more of these is to be selected. 
Actions taken 

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0 = No action taken 
1 = Concomitant medication taken 
2 = Non-drug therapy given 
3 = Hospitalization / prolonged hospitalization 
 
6.8 
Serious Adverse Events 
A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose:  
Definition 
• Results in death; 
• Is life threatening (at the time of the event); 
• Requires hospitalization or prolongation of existing inpatients’ hospitalization; 
• Results in persistent or significant disability or incapacity; 
• Is a congenital anomaly or birth defect; 
• Is an important medical event that satisfies any of the following: 
- 
May require intervention to prevent the items listed before 
- 
Is likely to affect the safety of the patient, even though the event is not immediately 
life threatening or fatal or does not result in hospitalization. 
 
In this study, the following hospitalizations will not
• Elective hospitalization for a pre-existing condition that has not worsened 
 lead to reporting of an SAE: 
• Hospitalization for logistical reasons 
• Hospitalization for study procedures 
 
All SAEs at any time during the study through the last follow-up visit required by the 
protocol must be reported by the investigator within 24 hours of knowledge of their 
occurrence to the sponsor or representative, independent of the circumstances or suspected 
cause. The report must be completed on the SAE report form in English and must include a 
relationship assessment. Information about every SAE will be collected and recorded on the 
SAE report form as well as in the eCRF, on the applicable AE page.  
Reporting serious adverse events 
The SAE report form should be sent by fax to Drug Safety Solutions, Inc (Raleigh, USA). 
SAE fax number: 
 
 
 
+1 919-844-6948 
Backup fax number:  
 
 
+1 919-882-8337 
Both the original and the duplicate NCR copy of the SAE report form, together with the fax 
confirmation sheet, must be kept at the study site. If the initial report is made verbally or by 
telephone, a written confirmation via fax must follow within 24 hours. The investigator will 

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be requested to supply detailed information regarding the event at the time of the initial 
report. 
Each SAE should be recorded as a single diagnosis on the SAE report form. Accompanying 
signs (including abnormal laboratory values and ECG findings) or symptoms should not
For all SAEs occurring during the study, the investigator must submit follow-up reports to 
the sponsor regarding the patient’s subsequent course until the SAE has resolved, or until the 
condition stabilizes (in the case of persistent impairment), or the patient dies. In the event 
that a patient dies, an autopsy report (if available) must be forwarded to Kiadis Pharma or its 
representative. The timelines and procedure for follow-up reports are the same as those for 
the initial report. The form and fax confirmation sheet must be retained by the site. 
 be 
recorded as additional SAEs. However, if the diagnosis is unknown, signs and symptoms 
should be recorded. As soon as the diagnosis causing the signs and symptoms is known, the 
event terms will be adjusted to the final diagnosis. 
All suspected unexpected serious adverse reactions (SUSARs) will be subject to expedited 
reporting to the regulatory authorities by the sponsor or its representative. The sponsor will 
also prepare expedited reports for other safety issues that might materially alter the current 
benefit-risk assessment of the investigational product. 
6.9 
Concomitant Medication Assessments 
The following concomitant medications must be recorded in the eCRF: 
• Medication for the treatment of GvHD 
• Medication for the treatment of infections, including prophylactic or preemptive use of 
anti-infective medication 
• Medication for the treatment of disease relapse 
• Medication for the treatment of other reported adverse events 
• Additional hematopoietic stem cell grafts 
• Additional lymphocyte infusions 
• Hematopoietic growth factors 
• Vaccinations 
 
6.10 Discontinuation of Patients from the Study 
Patients who are planned to receive two doses of ATIR101 and who receive only one dose, 
will not
Patients who do 
 be discontinued from the study, but will require the enrolment of an additional 
patient.  
not receive ATIR101 will be discontinued from the study and replaced by a 
new patient. In addition, the investigator may discontinue a patient from the study for any of 
the following reasons:  

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• The patient relapsed before collection of PBMCs for the manufacturing of ATIR101 and 
did not achieve remission upon additional chemotherapy, 
• The stem cell graft is not suitable for patient administration, 
• The patient requests to be withdrawn, or is unwilling or unable to comply with study 
requirements,  
• The patient is lost to follow-up, or 
• Any other reason which, in the opinion of the investigator, justifies discontinuation of the 
patient from the study. 
 
For any patient who is discontinued from the study, the reason must be recorded in the eCRF 
as end-of-study information.  
When a patient is discontinued from the study after having received a stem cell 
transplantation (with or without ATIR101 infusion), and if the patient agreed on the ICF, 
limited information on disease status, GvHD, and mortality at 6 and 12 months after the 
HSCT will be collected. If a patient is discontinued from the study after ATIR101 infusion, 
efforts will be made to report SAEs until at least 3 months after the infusion of ATIR101. 
If a patient for whom ATIR101 has been manufactured relapses before the HSCT, the patient 
is not necessarily discontinued from the study. The investigator may decide to keep the 
patient in the study without any follow-up visits if treatment with an HSCT followed by 
ATIR101 may be beneficial at a later stage. After re-assessment of patient eligibility the 
study schedule may be resumed if ATIR101 can still be administered within its shelf-life. 
In case it will be decided that the study will be prematurely terminated, all patients who are 
still in the study should at least complete the visit at Week 16 after the HSCT. After 
premature termination of the study, patients will be followed up for the occurrence of serious 
adverse events (SAEs) until 6 months after ATIR101 administration. 

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7 STUDY ASSESSMENTS BY VISIT 
Unless otherwise specified, study assessments in this section apply to the patient. See 
Appendix 1 for a tabulated schedule of study assessments. 
7.1 
Screening: Between Informed Consent and Apheresis 
• Informed consent patient and donor 
• Apheresis patient and donor 
• Patient characteristics and eligibility 
- 
Demographics  
- 
Hematologic malignancy  
- 
Medical history 
- 
Performance status 
- 
Physical examination 
- 
High resolution CT scan of the thorax (if not already done within 6 weeks before 
signing informed consent, unless the patient experienced a significant event between 
the date of the original assessment and the date of screening) 
- 
Echocardiogram/MUGA scan (if not already done within 6 weeks before signing 
informed consent, unless the patient experienced a significant event between the date 
of the original assessment and the date of screening) 
- 
Pulmonary function test (if not already done within 6 weeks before signing informed 
consent, unless the patient experienced a significant event between the date of the 
original assessment and the date of screening) 
- 
Creatinine clearance (calculated or measured, if not already done within 2 weeks 
before signing informed consent) 
- 
Pregnancy test; only for females who are not diagnosed as postmenopausal or who 
are surgically sterilized 
- 
Viral testing 
• Donor characteristics and eligibility 
- 
Demographics  
- 
HLA compatibility  
- 
Viral testing 
- 
Pregnancy test; only for female donors who are not diagnosed as postmenopausal or 
who are surgically sterilized 
• Donor adverse events 
• Vital signs 
• Safety laboratory tests 
- 
Hematology 
- 
Blood chemistry 
- 
Urinalysis 
• Efficacy and safety assessments 
- 
Immunophenotyping 
- 
Immunoglobulins 
- 
Serum sampling for additional assessments of immune reconstitution 

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- 
Infection assessment 
- 
Disease assessment 
A bone marrow aspirate and/or biopsy are performed if not already done within 
6 weeks before signing informed consent. 
- 
Other adverse events 
• Concomitant medications 
 
7.2 
HSCT (Day 0) 
• HSCT 
• Physical examination 
• Donor adverse events (until collection of stem cells) 
• Vital signs 
• Safety laboratory tests 
- 
Hematology 
- 
Blood chemistry 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
• Efficacy and safety assessments 
- 
Serum sampling for additional assessments of immune reconstitution 
- 
Infection assessment 
- 
Disease assessment  
- 
Other adverse events 
• Concomitant medications 
 
7.3 
Week 1, Week 2, and Week 3 
Visits must be performed within the following windows: 
• Week 1: 1 week ± 2 days after the HSCT 
• Week 2: 2 weeks ± 2 days after the HSCT 
• Week 3: 3 weeks ± 2 days after the HSCT 
 
• Weekly safety laboratory tests 
Study assessments: 
- 
Hematology 
- 
Blood chemistry 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
• Efficacy and safety assessments 
- 
Infection assessment 

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- 
Disease assessment  
- 
GvHD assessment 
- 
Other adverse events 
• Concomitant medications 
• Engraftment 
 
7.4 
First ATIR101 Infusion (Week 4) 
The visit must be performed within 28-32 days after the HSCT unless the patient's medical 
requires that ATIR101 is infused later, e.g. because the patient is suffering from acute GvHD. 
If the first ATIR101 infusion is postponed, the subsequent weekly visits will be moved 
accordingly and extra visits before the first ATIR101 infusion will be scheduled. 
• ATIR101 infusion 
Study assessments: 
• Physical examination 
• Vital signs before ATIR101 infusion 
In addition, following ATIR101 infusion, pulse rate and supine blood pressure will be 
assessed after 15 minutes, 1, 2, 3, and 4 hours. Continuous oxygen monitoring will be 
done if the patient has respiratory problems. 
• Safety laboratory tests 
- 
Hematology 
- 
Blood chemistry 
- 
Urinalysis 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
- 
Chimerism before ATIR101 infusion 
• Efficacy and safety assessments 
- 
Immunophenotyping before ATIR101 infusion 
- 
Immunoglobulins before ATIR101 infusion 
- 
Serum sampling for additional assessments of immune reconstitution; before 
ATIR101 infusion 
- 
Infection assessment 
- 
Disease assessment  
- 
GvHD assessment 
- 
Other adverse events 
• Concomitant medications 
 
7.5 
Week 5, Week 6, Week 7, Week 8, and Week 9 
Visits must be performed within the following windows: 
• Week 5: 5 weeks ± 2 days after the HSCT 

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• Week 6: 6 weeks ± 2 days after the HSCT 
• Week 7: 7 weeks ± 2 days after the HSCT 
• Week 8: 8 weeks ± 2 days after the HSCT 
• Week 9: 9 weeks ± 2 days after the HSCT 
 
• Physical examination, only at Week 6 and Week 8 
Study assessments: 
• Vital signs 
• Safety laboratory tests 
- 
Hematology 
- 
Blood chemistry 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated   
• Efficacy and safety assessments 
- 
Immunophenotyping, only at Week 5, Week 7, and Week 9 
- 
Serum sampling for measuring cytokine levels and/or immunoglobulins against 
specific antigens, only at Week 5, Week 7, and Week 9 
- 
Peripheral blood sampling for measuring pathogen-specific T-cells, only at Week 6 
- 
Infection assessment 
- 
Disease assessment  
- 
GvHD assessment 
- 
Other adverse events 
• Concomitant medications 
 
7.6 
Second ATIR101 Infusion (Week 10) 
The visit must be performed 70-74 days after the HSCT but at least 42 days after the first 
ATIR101 infusion, unless the patient's medical condition requires that ATIR101 is infused 
later, e.g. because the patient is suffering from acute GvHD. If the second ATIR101 infusion 
is postponed, the subsequent weekly visits will be moved accordingly and one or more 
unscheduled visits may be added before the second ATIR101 infusion. 
• ATIR101 infusion  
Study assessments: 
• Physical examination 
• Vital signs before ATIR101 infusion 
In addition, following ATIR101 infusion, pulse rate and supine blood pressure will be 
assessed after 15 minutes, 1, 2, 3, and 4 hours. Continuous oxygen monitoring will be 
done if the patient has respiratory problems. 
• Safety laboratory tests 
- 
Hematology 

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- 
Blood chemistry 
- 
Urinalysis 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
- 
Chimerism before ATIR101 infusion 
• Efficacy and safety assessments 
- 
Immunophenotyping before ATIR101 infusion 
- 
Immunoglobulins before ATIR101 infusion 
- 
Serum sampling for measuring cytokine levels and/or immunoglobulins against 
specific antigens; before ATIR101 infusion 
- 
Infection assessment 
- 
Disease assessment  
- 
GvHD assessment 
- 
Other adverse events 
• Concomitant medications 
 
7.7 
Week 11, Week 12, Week 13, Week 14, Week 15, and Week 16 
Visits must be performed within the following windows: 
• Week 11: 11 weeks ± 2 days after the HSCT 
• Week 12: 12 weeks ± 2 days after the HSCT 
• Week 13: 13 weeks ± 2 days after the HSCT 
• Week 14: 14 weeks ± 2 days after the HSCT 
• Week 15: 15 weeks ± 2 days after the HSCT 
• Week 16: 16 weeks ± 2 days after the HSCT 
 
• Physical examination, only at Week 12, Week 14, and Week 16 
Study assessments: 
• Vital signs 
• Safety laboratory tests 
- 
Hematology 
- 
Blood chemistry 
- 
Urinalysis, only at Week 16 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
• Efficacy and safety assessments 
- 
Immunophenotyping 
- 
Immunoglobulins, only at Week 11, Week 13, and Week 16 
- 
Serum sampling for measuring cytokine levels and/or immunoglobulins against 
specific antigens 

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- 
Peripheral blood sampling for measuring pathogen-specific T-cells, only at Week 12 
- 
Infection assessment 
- 
Disease assessment 
- 
GvHD assessment 
- 
Other adverse events 
• Concomitant medications 
 
7.8 
Month 5, Month 6, Month 9, and Month 12 
Visits must be performed within the following windows: 
• Month 5 after HSCT: 5 months ± 1 week after the HSCT 
• Month 6 after HSCT: 6 months ± 1 week after the HSCT 
• Month 9 after HSCT: 9 months ± 2 weeks after the HSCT 
• Month 12 after HSCT: 12 months ± 2 weeks after the HSCT 
 
• Safety laboratory tests 
Study assessments: 
- 
CMV monitoring (PCR) 
- 
EBV monitoring (PCR), if donor or patient is EBV positive before HSCT or as 
indicated 
• Efficacy and safety assessments 
- 
Immunophenotyping 
- 
Immunoglobulins 
- 
Serum sampling for measuring cytokine levels and/or immunoglobulins against 
specific antigens 
- 
Peripheral blood sampling for measuring pathogen-specific T-cells, only at Month 6 
and Month 12 
- 
Infection assessment 
- 
Disease assessment 
At Month 6 and Month 12 a bone marrow aspirate and/or biopsy are performed 
(unless relapse has already been confirmed and if not already done within 6 weeks 
before the visit). 
- 
GvHD assessment 
• Concomitant medications 
 

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7.9 
End of Study 
When a patient discontinues from the study the primary reason for study withdrawal is 
recorded along with the date of study discontinuation (see also Section 6.10). 
When a patient is discontinued from the study after having received a stem cell 
transplantation (with or without ATIR101 infusion), and if the patient agreed on the ICF, 
limited information on disease status, GvHD, and mortality at 6 and 12 months after the 
HSCT will be collected.  

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8 QUALITY CONTROL AND ASSURANCE 
8.1 
ATIR101 Manufacturing 
ATIR101 will be manufactured as individualized patient batches at a manufacturing facility, 
under supervision of Kiadis Pharma. Before start of the study, Kiadis Pharma Quality 
Assurance (QA) will qualify the manufacturing facility including its quality system. The 
qualification program includes site visit(s), verification audit(s), and the generation of a 
quality agreement between Kiadis Pharma and the manufacturing facility.  
Kiadis Pharma will train personnel from the manufacturing facility in the optimized process 
used in study CR-AIR-008. The manufacturing batch records will be subject of a separate 
training by experts from Kiadis Pharma. 
Quality Control (QC) testing of ATIR101, the raw (starting) materials and intermediates will 
be performed at the manufacturing facility, contract laboratories, and/or the Kiadis Pharma 
R&D laboratory. Contract laboratories will be qualified by Kiadis Pharma QA prior to the 
start of ATIR101 manufacturing. 
Because ATIR101 is manufactured as individualized patient batches and for every patient a 
different patient-donor combination is used, there is a chance that a batch fails to meet the 
acceptance criteria for administration within this study protocol. These cases will be 
discussed and trended in Quality Review Meetings, during which appropriate follow-up 
measures will be initiated. 
8.2 
Clinical Study 
Procedures relevant to the clinical management of this study are either described in the 
applicable Standard Operating Procedures (SOPs), or in the project manual. The purpose of 
the project manual is to describe all procedures which have not been covered in the SOPs. If 
new SOPs are generated or updated during the course of the study, the project manual will be 
updated and reference will be made to the new SOP. 
Kiadis Pharma will not allow any waivers to the applicable protocol throughout the conduct 
of the study. An unplanned excursion from the protocol not implemented or intended as a 
systematic change, which could not be justified as necessary to protect the safety, rights, or 
welfare of the subjects, will be reported and followed up according to the local IEC 
requirements. For deviations from the approved protocol see also Section 10.9. 
In accordance with Kiadis Pharma procedures, this study may be subject to an independent 
QA GCP audit and/or a sponsor initiated inspection at the study sites. 

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9 PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
Details of the planned analyses will be described in a statistical analysis plan (SAP). Any 
deviations from the SAP will be justified in the clinical study report. 
9.2 
Determination of Sample Size 
In this exploratory study, 15 patients with a hematologic malignancy who are eligible for a 
haploidentical HSCT will be treated with two doses of ATIR101. This sample size has been 
calculated with the following formula based on the primary endpoint (incidence of acute 
GvHD grade III/IV up to 180 days post HSCT): 
𝑛> ൬𝑧∗
𝑚൰
2
 𝑝∗ (1 −𝑝∗) 
where n = sample size 
z* = z-value related to confidence interval, i.e. 1.645 for a one-sided 95% confidence interval 
m = desired margin of error, i.e. 13% 
p* = estimated population proportion, i.e. 10% acute GvHD grade III/IV 180 days post HSCT 
9.3 
Analysis Populations  
All patients who provided informed consent and received an HSCT will be included in the 
analyses. The following analysis populations will be discerned: 
The ITT population consists of all enrolled patients who received an HSCT whether or not 
they received ATIR101.  
Intention-to-treat (ITT) population  
The MITT population consists of all ITT patients who received at least one dose of 
ATIR101. The primary analyses will be conducted using the MITT population. 
Modified intention-to-treat (MITT) population  
The PP population consists of all patients who: 
Per protocol (PP) population 
• Received the first ATIR101 between 28 and 42 days after the HSCT,  
• Received the second ATIR101 infusion between 70 and 84 days after the HSCT (if they 
received a second ATIR101 infusion),  

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• Showed hematologic engraftment (neutrophil count ≥ 0.5×109/L for 2 consecutive days 
and platelets ≥ 20×109/L for 3 consecutive days, without transfusion) at the time of the 
first ATIR101 infusion (see Section 5.2), and 
• Did not present any major protocol deviations (see Section 10.9).  
 
The safety population will include all patients who received an HSCT and provided informed 
consent. 
Safety population  
9.4 
Demographics and Baseline Characteristics 
Descriptive statistics will be provided for demographics and other baseline characteristics. 
9.5 
Primary Endpoint (Safety) 
The primary endpoint will be the incidence of acute graft versus host disease (GvHD) grade 
III/IV up to 180 days post HSCT. Therefore, the primary analysis will be based on the data at 
180 days after the HSCT. 
From the assumptions in Section 9.2 it can be derived that the study fails if the incidence of 
acute GvHD grade III/IV up to 180 days post HSCT in the MITT population exceeds 23% 
(desired margin of error + estimated population proportion). 
9.6 
Secondary Endpoints 
In this study the following secondary endpoints up to 12 months post HSCT have been 
identified: 
• Incidence and severity of acute and chronic graft versus host disease (GvHD)  
• Time to T-cell reconstitution, defined as the time to CD3+ in peripheral blood higher than 
0.2×109/L (at two consecutive measurements; time to first measurement) 
• Incidence and severity of viral, fungal, and bacterial infections 
• Transplant-related mortality (TRM), defined as death due to causes other than disease 
relapse or progression, or other causes which are unrelated to the transplantation 
procedure (e.g. accident, suicide) 
• Relapse-related mortality (RRM), defined as death due to disease relapse or disease 
progression 
• Overall survival (OS), defined as the time from HSCT until death from any cause 
• Progression-free survival (PFS), defined as the time from HSCT until relapse, disease 
progression, or death, whichever occurs first 
• GvHD-free, relapse-free survival (GRFS), defined as the time until acute GvHD 
grade III/IV, chronic GvHD requiring systemic treatment, relapse, or death, whichever 
occurs first (Holtan et al. 2015) 
 

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All endpoints will be analyzed using descriptive statistics. Immune reconstitution will be 
graphically displayed in time. The Kaplan-Meier method will be used to display and estimate 
probability of time-related survival data (OS, PFS, GRFS). In addition, cumulative incidence 
curves taking into account competing risks will be used to display and estimate cumulative 
incidences of TRM, RRM, and GvHD. 

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10 ADMINISTRATIVE CONSIDERATIONS 
10.1 Independent Ethics Committee (IEC) Approval 
The study protocol and any amendments must be reviewed by an appropriate independent 
ethics committee (IEC) that is constituted and operating in accordance with Good Clinical 
Practice (GCP) and applicable national/local laws and regulations. The study may only start 
after receipt of written IEC approval by the sponsor.  
10.2 Ethical Conduct of the Study 
The study will be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki (and all amendments thereof) and that are consistent with the 
current International Conference on Harmonization (ICH) Guideline for Good Clinical 
Practice (Topic E6 [R1]) as well as the applicable regulatory requirements. 
10.3 Patient and Donor Information and Consent 
• The informed consent forms and any other written study materials provided to the 
patients and donors have to be approved by an IEC before patient enrollment. 
• The investigator/sub-investigator is responsible for explaining the nature and purpose of 
the study as well as other study-related matters to patients and donors, using the written 
information, and for obtaining their full understanding and written consent to participate 
in the study at their own free will. 
• The investigator or other responsible personnel who provided explanations to the patient 
and the donor (including collaborators who gave supportive information, if applicable), 
should sign and date the written information. 
• In case of a donor under age, the donor as well as his/her legal representative should be 
informed about the study and must sign and date the written information. 
• Informed consent must be obtained prior to the first observations/examinations of the 
screening period are performed (use of assessments which were performed before signing 
informed consents is subject of informed consent).  
• The investigator or other responsible personnel must give a copy of the signed consent 
form to the patient and the donor and store the original. 
• The process and communication of the consent should be documented on medical records 
of the patient and donor.  
• The investigator or other responsible personnel should note the following when obtaining 
consent from patients and donors: 
- 
No patient/donor may be subjected to undue influence, such as compulsory 
enrollment into a study. 
- 
The language and expressions used in the written information should be as plain and 
understandable as possible. Patients should be given the opportunity to ask questions 
and receive satisfactory answers to the inquiry, and should have adequate time to 
decide whether or not to participate in the study. Written information should not 
contain any language or contents that causes the patient to waive or appears to waive 
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the investigator/sub-investigator, collaborators, or the sponsor from liability for 
negligence. 
 
The signed consent forms will be retained by the investigator and made available (for review 
only) to the study monitor, and auditor upon request. 
• The investigator/sub-investigator should immediately inform the patient orally whenever 
new information becomes available that may be relevant to the patient’s consent or may 
influence the patient’s willingness to continue participation in the study (e.g., report of 
serious adverse drug reactions). The communication should be documented on medical 
records, for example, and it should be confirmed whether the patient is willing to remain 
in the study or not.  
Supply of new and important information influencing the patient’s consent and revision of 
the written information 
• If the investigator or the sponsor recognizes the necessity to revise the written 
information in the terms and conditions applicable to the first point, the written 
information should be revised immediately based on the newly available information, and 
be re-approved by the IEC.  
• The investigator/sub-investigator should obtain written informed consent to continue 
participation with the revised written information defined in the previous bullet even if 
patients are already informed of the relevant information orally. The investigator or other 
responsible personnel who provided explanations and the patient and donor should sign 
and date the informed consent form. The investigator or other responsible personnel 
should give a copy of the signed informed consent form to the patient and donor who had 
given consent with the written information and store the original appropriately as done 
for the first informed consent.  
 
10.4 Patient Confidentiality 
The information obtained during the conduct of this clinical study is confidential, and 
disclosure to third parties other than those noted below is strictly prohibited. Upon the 
patient’s permission, medical information may be given to his or her personal physician or 
other appropriate medical personnel responsible for his or her medical welfare.  
Kiadis Pharma will use the information obtained during the conduct of this study for the 
development of ATIR101. The study investigator is obliged to provide Kiadis Pharma with 
complete test results and all data developed in this study, as described in this protocol. This 
information may be disclosed to appropriate Competent Authorities. 
Even though individuals involved in the study, including the study monitors and auditors, 
may get to know matters related to patients’ privacy due to direct access to source 
documents, or from other sources, they may not disclose the contents to third parties.  

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Data generated by this study must be available for inspection upon request by representatives 
of the EMA, the FDA, Health Canada, any other Competent Authority, IECs (if appropriate), 
and Kiadis Pharma. 
ICH guidelines for Good Clinical Practice require that all records and documents pertaining 
to the conduct of this study and the distribution of investigational drug, including eCRFs, 
consent forms, laboratory tests, and medication inventory records, must be retained by the 
Investigator until at least 2 years after the last approval of a marketing application in an ICH 
region and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents must be retained for a longer 
period, however, if required by the applicable regulatory requirements or by an agreement 
with Kiadis Pharma. It is the responsibility of Kiadis Pharma to inform the Investigator as to 
when these documents no longer need to be retained. 
10.5 Study Monitoring 
Kiadis Pharma is responsible for monitoring the clinical study to ensure that patients’ human 
rights, safety, and well-being are protected, that the study is properly conducted in adherence 
to the current protocol, to GCP, and to applicable regulatory requirements, and that study 
data reported by the investigator/sub-investigator are accurate and complete and that they are 
verifiable with study-related records such as source documents. The sponsor will determine 
the extent and nature of the monitoring and assign clinical monitor(s). The sponsor will 
provide the monitor(s) with adequate training on the study protocol. The study will be 
monitored in accordance with the clinical monitoring plan. 
10.6 Electronic Case Report Forms and Study Records 
The investigator or designee must enter all protocol-required data in the available electronic 
case report form (eCRF). An eCRF will be developed for both the patient and the donor. In 
the interest of collecting data in the most efficient manner, the investigator or designee 
should enter data (including laboratory values) into the eCRF as soon as possible after the 
patient’s visit. The eCRFs and any supporting documents should be available for retrieval at 
any given time. The monitor should verify the data in the eCRFs with source documents and 
confirm that there are no inconsistencies between them. If the monitor finds no 
inconsistencies, the appropriate eCRF parts are electronically signed. If any inconsistency is 
detected on the eCRFs, the monitor must query the investigator and the investigator should 
make corrections/additions in the eCRF or provide an explanation within the eCRF system. 
The monitor should verify the corrected data with source documents to confirm that there are 
no inconsistencies between them, and also check that appropriate records on the 
corrections/additions of data are maintained. 
For screening failures, defined as patients who signed informed consent but were not eligible 
for study participation, the minimum demographic data (date of birth and gender) and reason 
for withdrawal will also be collected in an eCRF. 

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The investigator is responsible to ensure that all data in the eCRFs are accurate and complete, 
and that all entries are verifiable with source documents. Source data must be available at the 
site to document the existence of the study patients and donors, and substantiate the integrity 
of study data collected. In case a patient is prematurely discontinued, the reason for 
discontinuation must be documented in the source documents. 
10.7 Independent Data Monitoring Committee 
An independent data monitoring committee (IDMC) will be established to monitor the safety 
of the patients in study CR-AIR-008. The IDMC will consist of three members, who are not 
affiliated to the sponsor. The members of the IDMC are responsible for safeguarding the 
interests of the patients by reviewing the safety and mortality data during the study. The 
IDMC will serve as an independent advisory group to the sponsor and is required to provide 
recommendations about continuing (with or without modifications) or stopping the study. 
Procedures to be used for the IDMC, including composition and roles and responsibilities of 
its members, will be described in detail in the IDMC charter. 
10.8 Adjudication Committees 
In order to obtain objective clinical GvHD and mortality data two adjudication committees 
will be established: 
• To ensure a more objective approach for the classification and severity grading of 
GvHD events, Kiadis Pharma will request an independent GvHD adjudication 
committee to review each (possible) GvHD case and to come to a final assessment for 
GvHD classification and severity grading together with the treating investigator. If 
this final GvHD assessment is different from the assessment made earlier by the 
treating investigator, the eCRF will be adjusted according to the final assessment 
agreed upon. Procedures to be used for the GvHD adjudication committee will be 
described in detail in a separate charter. 
• To ensure an objective assessment of the classification of the cause of death, Kiadis 
Pharma will request an independent death adjudication committee to review each 
death case and to provide a final assessment for the cause of death. This final 
assessment will be recorded on a separate CRF page and will be added to the clinical 
database. Procedures to be used for the death adjudication committee will be 
described in detail in a separate charter. 
10.9 Major Protocol Deviations 
In this study the following deviations from the protocol will be considered major protocol 
deviations and will be reported as such in the clinical study report: 
• Non-adherence to inclusion/exclusion criteria 
• Patient suffering from active GvHD (any grade) at the time of ATIR101 infusion (see 
Section 5.2) 

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• Patient having received steroid-based immunosuppressive therapy (excluding topical 
steroids) at the time of ATIR101 infusion (see Section 5.2). 
• Patient received an unmanipulated DLI (see Section 5.6.3) 
 
10.10 Access to Source Documentation 
The investigator and the study site must accept monitoring and auditing by Kiadis Pharma or 
their representatives as well as inspections from the IEC and relevant regulatory authorities. 
In these instances, they must provide all study-related records, such as source documents 
when they are requested by the monitors and auditors, the IEC, or regulatory authorities. The 
confidentiality of the patients’ identities shall be well protected consistent with local and 
national regulations when the source documents are subject to direct access. 
10.11 Data Generation and Analysis 
Data management will be coordinated by a delegated CRO, in accordance with their SOPs 
for data management. All study specific processes and definitions will be described in the 
data management plan (DMP). Coding of medical terms will be performed using MedDRA.  
10.12 Retention of Data 
All essential documents as defined by ICH-GCP must be retained by the investigator for as 
long as necessary to comply with national and international regulations but at least 2 years 
after the last marketing approval or after discontinuation of clinical development. Kiadis 
Pharma will notify the investigators when the investigator study file is no longer needed. 
10.13 Financial Disclosure 
The investigators have no disclosable financial interests in or arrangements with the sponsor 
of this clinical study, i.e. Kiadis Pharma Netherlands B.V. 
10.14 Publication and Disclosure Policy 
The sites and the principal investigators shall have the right to publish and present results of 
the study following submission to Kiadis Pharma Netherlands B.V. for review of the 
manuscript, abstract or presentation intended for publication or presentation at least 70 days 
prior to the date of submission for publication or presentation. Kiadis Pharma Netherlands 
B.V. shall complete its review within 60 days of receipt of the submitted manuscript, abstract 
or presentation. Kiadis Pharma Netherlands B.V. may request that the principal investigators 
or the sites delete from the manuscript, abstract or presentation any confidential information. 
At the end of the 60-day period, the sites and the principal investigators will have the right to 
publish and present the material, abstract and presentation. However, single site data may not 
be published and/or presented prior to the publication of the multicenter data from the overall 
study. 
Publication policy 

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Confidential 
Page 59 of 75 
 
Information concerning the study drug, patent applications, processes, unpublished scientific 
data, the Investigator's Brochure and other pertinent information is confidential and remains 
the property of the sponsor. Details should be disclosed only to the persons involved in the 
approval or conduct of the study. The investigator may use this information for the purpose 
of the study only. It is understood by the investigator that the sponsor will use the 
information obtained during the clinical study in connection with the development of the 
drug and therefore may disclose it as required to other clinical investigators or to regulatory 
agencies. In order to allow for the use of the information derived from this clinical study, the 
investigator understands that he/she has an obligation to provide the sponsor with all data 
obtained during the study. 
Disclosure policy 

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Clinical Study Protocol: CR-AIR-008 (after Amendment 1) 
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11 REFERENCE LIST 
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Pharmacol 2002; 2(4):452-457. 
Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of 
high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully 
mismatched HLA haplotype. N Engl J Med 1998; 339(17):1186-1193. 
Boumedine RS, Krosl G, Vaillancourt M, Perreault C, Roy DC. Specific Elimination of 
Alloreactive T Lymphocytes Using Photodynamic Therapy Prevents GVHD and Enables 
Rapid Immune Reconstitution. ASH Annual Meeting Abstracts 2004; 104(11):4987. 
Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J et al. Alternative donor 
transplantation after reduced intensity conditioning: results of parallel phase 2 trials using 
partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood 
grafts. Blood 2011; 118(2):282-288. 
Champlin R, Hesdorffer C, Lowenberg B, Martelli MF, Mertelsmann RH, Reisner Y et al. 
Haploidentical 'megadose' stem cell transplantation in acute leukemia: recommendations for 
a protocol agreed upon at the Perugia and Chicago meetings. Leukemia 2002; 16(3):427-428. 
Ciceri F, Bonini C, Marktel S, Zappone E, Servida P, Bernardi M et al. Antitumor effects of 
HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood 
2007; 109(11):4698-4707. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976; 16(1):31-41. 
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National 
Institutes of Health consensus development project on criteria for clinical trials in chronic 
graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow 
Transplant 2005; 11(12):945-956. 
Franzke A, Piao W, Lauber J, Gatzlaff P, Konecke C, Hansen W et al. G-CSF as immune 
regulator in T cells expressing the G-CSF receptor: implications for transplantation and 
autoimmune diseases. Blood 2003; 102(2):734-739. 
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical 
manifestations of graft-versus-host disease in human recipients of marrow from HL-A-
matched sibling donors. Transplantation 1974; 18(4):295-304. 
Goker H, Haznedaroglu IC, Chao NJ. Acute graft-vs-host disease: pathobiology and 
management. Exp Hematol 2001; 29(3):259-277. 
Gratwohl A. The EBMT risk score. Bone Marrow Transplant 2012; 47(6):749-756. 

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Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A, Niederwieser D. Results of 
the EBMT activity survey 2005 on haematopoietic stem cell transplantation: focus on 
increasing use of unrelated donors. Bone Marrow Transplant 2007; 39(2):71-87. 
Guimond M, Balassy A, Barrette M, Brochu S, Perreault C, Roy DC. P-glycoprotein 
targeting: a unique strategy to selectively eliminate immunoreactive T cells. Blood 2002; 
100(2):375-382. 
Guimond M, Brochu S, Perreault C, Molfino N, Roy DC. Specific elimination of anti-host 
alloreactivity using a photodynamic approach. FASEB J 2000; 14:A1074. 
Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG et al. Composite 
end point of graft-versus-host disease-free, relapse-free survival after allogeneic 
hematopoietic cell transplantation. Blood 2015; %19;125(8):1333-1338. 
Horwitz ME, Sullivan KM. Chronic graft-versus-host disease. Blood Rev 2006; 20(1):15-27. 
Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS et al. Risk factors for 
acute GVHD and survival after hematopoietic cell transplantation. Blood 2012; 119(1):296-
307. 
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW et al. National 
Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic 
Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol 
Blood Marrow Transplant 2015; 21(3):389-401. 
Kanakry CG, Tsai HL, Bolanos-Meade J, Smith BD, Gojo I, Kanakry JA et al. Single-agent 
GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-
matched BMT for AML, ALL, and MDS. Blood 2014; 124(25):3817-3827. 
Koh LP, Rizzieri DA, Chao NJ. Allogeneic hematopoietic stem cell transplant using 
mismatched/haploidentical donors. Biol Blood Marrow Transplant 2007; 13(11):1249-1267. 
Lewalle P, Triffet A, Delforge A, Crombez P, Selleslag D, De Muynck H. et al. Donor 
lymphocyte infusions in adult haploidentical transplant: a dose finding study. Bone Marrow 
Transplant 2003; 31(1):39-44. 
Ljungman P, Urbano-Ispizua A, Cavazzana-Calvo M, Demirer T, Dini G, Einsele H et al. 
Allogeneic and autologous transplantation for haematological diseases, solid tumours and 
immune disorders: definitions and current practice in Europe. Bone Marrow Transplant 2006; 
37(5):439-449. 
Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R et al. High-dose 
cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. 
Blood 2010; 115(16):3224-3230. 

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Martino R, Romero P, Subira M, Bellido M, Altes A, Sureda A et al. Comparison of the 
classic Glucksberg criteria and the IBMTR Severity Index for grading acute graft-versus-host 
disease following HLA-identical sibling stem cell transplantation. International Bone 
Marrow Transplant Registry. Bone Marrow Transplant 1999; 24(3):283-287. 
Michallet M, Sobh M, Milligan D, Morisset S, Niederwieser D, Koza V et al. The impact of 
HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell 
transplantation for CLL: a retrospective study from the EBMT registry. Leukemia 2010; 
24(10):1725-1731. 
Mielke S, Nunes R, Rezvani K, Fellowes VS, Venne A, Solomon SR et al. A clinical-scale 
selective allodepletion approach for the treatment of HLA-mismatched and matched donor-
recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-
based photodepletion technique. Blood 2008; 111:4392-4402. 
Pasquini M, Zhu X. Current uses and outcomes of hematopoietic stem cell transplantation: 
2014 CIBMTR Summary Slides. Available at: http://www.cibmtr.org . 2015.  
Przepiorka D, Weisdorf D, Martin P, Klingemann H-G, Beatty P, Hows J et al. Consensus 
conference on acute GVHD grading. Bone Marrow Transplantation 1995; 15:825-828. 
Ruggeri L, Aversa F, Martelli MF, Velardi A. Allogeneic hematopoietic transplantation and 
natural killer cell recognition of missing self. Immunol Rev 2006; 214:202-218. 
Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, 
validity, and guidelines. J Clin Oncol 1984; 2(3):187-193. 
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic 
cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before 
allogeneic HCT. Blood 2005; 106(8):2912-2919. 
Tabilio A, Falzetti F, Zei T, De Ioanni M, Bonifacio E, Battelli F et al. Graft engineering for 
allogeneic haploidentical stem cell transplantation. Blood Cells, Molecules, and Diseases 
2004; 33(3):274-280. 
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 
revision of the World Health Organization (WHO) classification of myeloid neoplasms and 
acute leukemia: rationale and important changes. Blood 2009; 114(5):937-951. 
Vogelsang GB. How I treat chronic graft-versus-host disease. Blood 2001; 97(5):1196-1201. 
 
 

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Appendix 1 
Schedule of Study Assessments 
 
Screening: 
between 
informed 
consent & 
apheresis 
HSCT 
(Day 0) 
Week  
1, 2, 3 
1st 
ATIR101 
infusion 
Week 4 
Week  
5, 6, 7, 8, 9 
2nd 
ATIR101 
infusion 
Week 10 
Week  
11, 12, 13, 
14,15, 16 
Month  
5, 6, 9, 12 
Informed consent patient and donor 
X 
 
 
 
 
 
 
 
Apheresis patient and donor 
X 
 
 
 
 
 
 
 
HSCT 
 
X 
 
 
 
 
 
 
ATIR101 infusion 
 
 
 
X 
 
X 
 
 
Patient characteristics and 
eligibility 
 
Demographics 
X 
 
 
 
 
 
 
 
Hematologic malignancy 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
X 
X 1
X 
 
X 2
 
 
High resolution CT scan of the thorax 
X 3 
 
 
 
 
 
 
 
Echocardiogram/MUGA scan 
X 3
 
 
 
 
 
 
 
 
Pulmonary function test 
X 3 
 
 
 
 
 
 
 
Creatinine clearance 
X 4
 
 
 
 
 
 
 
 
Pregnancy test  
X 
 
 
 
 
 
 
 
Viral testing 
X 
 
 
 
 
 
 
 
 
1  
Only at Week 6 and Week 8 
2  
Only at Week 12, Week 14, and Week 16 
3  
If not already done within 6 weeks before signing informed consent 
4  
Calculated or measured, if not already done within 2 weeks before signing informed consent 

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Screening: 
between 
informed 
consent & 
apheresis 
HSCT 
(Day 0) 
Week  
1, 2, 3 
1st 
ATIR101 
infusion 
Week 4 
Week  
5, 6, 7, 8, 9 
2nd 
ATIR101 
infusion 
Week 10 
Week  
11, 12, 13, 
14,15, 16 
Month  
5, 6, 9, 12 
Donor characteristics and eligibility 
 
Demographics 
X 
 
 
 
 
 
 
 
HLA compatibility 
X 
 
 
 
 
 
 
 
Pregnancy test 
X 
 
 
 
 
 
 
 
Viral testing 
X 
 
 
 
 
 
 
 
Donor adverse events 
X 
X 1
 
 
 
 
 
 
 
Vital signs 
X 
X 
 
X 2
X 
 
X 2 
X 
 
Safety laboratory tests 
 
Hematology 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
X 
 
X 
X 3
 
 
CMV monitoring (PCR) 
 
X 
X 
X 
X 
X 
X 
X 
EBV monitoring (PCR) 4
 
 
X 
X 
X 
X 
X 
X 
X 
Engraftment 
 
 
X 
 
 
 
 
 
Chimerism 
 
 
 
X 5
 
 
X 5 
 
 
 
1  
Until collection of stem cells 
2  
Before ATIR101 infusion. In addition, following ATIR101 infusion, pulse rate and supine blood pressure will be assessed after 15 minutes, 1, 2, 3, and 
4 hours. Continuous oxygen monitoring will be done if the patient has respiratory problems. 
3  
Only at Week 16 
4  
If donor or patient is EBV positive before HSCT or as indicated 
5  
Before ATIR101 infusion 

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Screening: 
between 
informed 
consent & 
apheresis 
HSCT 
(Day 0) 
Week  
1, 2, 3 
1st 
ATIR101 
infusion 
Week 4 
Week  
5, 6, 7, 8, 9 
2nd 
ATIR101 
infusion 
Week 10 
Week  
11, 12, 13, 
14,15, 16 
Month  
5, 6, 9, 12 
Efficacy and safety assessments 
 
Immunophenotyping 
X 
 
 
X 1
X 
 
2 
X 1 
X 
X 
Immunoglobulins 
X 
 
 
X 1 
 
X 1 
X 3 
X 
Serum sampling 4
X 
 
X 
 
X 1 
X 2 
X 1 
X 
X 
Peripheral blood sampling 5
 
 
 
 
 
X 6 
 
X 6
X 
 
6 
Infection assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Disease assessment 7
X  
 
X 
X 
X 
X 
X 
X 
X 
GvHD assessment 
 
 
X 
X 
X 
X 
X 
X 
Mortality 
Continuous recording 
Other adverse events 
X 
X 
X 
X 
X 
X 
X 
 
Serious adverse events  
Continuous recording 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
. 
 
1  
Before ATIR101 infusion 
2  
Only at Week 5, Week 7, and Week 9 
3  
Only at Week 11, Week 13, and Week 16 
4  
For measuring cytokine levels and/or immunoglobulins against specific antigens 
5  
For measuring pathogen-specific T-cells 
6  
Only at Week 6, Week 12, Month 6, and Month 12 
7  
Includes bone marrow aspirate and/or biopsy at Screening, Month 6 and 12 after HSCT unless relapse has already been confirmed, and in case of suspected 
relapse 

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Appendix 2 
EBMT Risk Score 
 
EBMT risk score = sum of the scores for each of the five risk factors  
 
 
Risk factor 
0 points 
1 point 
2 points 
Age (yr) 
< 20 
20 - 40 
> 40 
Disease stage * 
Early 
Intermediate 
Late 
Time interval from diagnosis 
to transplant (months) 
< 12 
> 12 
- 
Donor type 
HLA- identical 
sibling 
Unrelated donor, 
other 
- 
Donor recipient sex 
combination 
Any other 
combination 
Female donor, 
male recipient 
- 
 
 
* Classification of disease stage for calculation of EBMT risk score 
Disease stage 
ALL, AML 
MDS 
Early 
In first complete remission 
Untreated or in first complete remission 
Intermediate 
In second complete remission 
In second complete remission or in 
partial remission 
Late 
In all other disease stages 
In all other disease stages 
 

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Appendix 3 
Hematopoietic Cell Transplantation-specific Comorbidity Index 
(HCT-CI) 
Comorbidity 
Definition of comorbidities 
HCT-CI 
weighted 
score 
Arrhythmia 
Atrial fibrillation or flutter, sick sinus syndrome, or ventricular 
arrhythmias 
1 
Cardiac 
Coronary artery disease*, congestive heart failure, myocardial 
infarction, or EF 
50% 
1 
Inflammatory bowel disease Crohns disease or ulcerative colitis 
1 
Diabetes 
Requiring treatment with insulin or oral hypoglycemics but not diet 
alone 
1 
Cerebrovascular disease 
Transient ischemic attack or cerebrovascular accident 
1 
Psychiatric disturbance 
Depression or anxiety requiring psychiatric consult or treatment 
1 
Hepatic, mild 
Chronic hepatitis, bilirubin > ULN to 1.5 x ULN, or AST/ALT > 
ULN to 2.5 x ULN 
1 
Obesity 
Patients with a body mass index > 35 kg/m2 
1 
Infection 
Requiring continuation of antimicrobial treatment after day 0 
1 
Rheumatologic 
SLE, RA, polymyositis, mixed CTD, or polymyalgia rheumatica 
2 
Peptic ulcer 
Requiring treatment 
2 
Moderate/severe renal 
Serum creatinine > 2 mg/dL, on dialysis, or prior renal 
transplantation 
2 
Moderate pulmonary 
DLCO and/or FEV1 66%-80% or dyspnea on slight activity 
2 
Prior solid tumor 
Treated at any time point in the patient's past history, excluding 
nonmelanoma skin cancer 
3 
Heart valve disease 
Except mitral valve prolapse 
3 
Severe pulmonary 
DLCO and/or FEV1 
65% or dyspnea at rest or requiring oxygen 
3 
Moderate/severe hepatic 
Liver cirrhosis, bilirubin > 1.5 x ULN, or AST/ALT > 2.5 x ULN 
3 
*One or more vessel-coronary artery stenosis requiring medical treatment, stent, or bypass graft. 
EF indicates ejection fraction; ULN, upper limit of normal; SLE, systemic lupus erythmatosis; RA, rheumatoid 
arthritis; CTD, connective tissue disease; DLCO, diffusion capacity of carbon monoxide. 
 
HCT-CI summary score is based on the sum of the HCT-CI weighted scores (Sorror et al. 
2005). 

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Appendix 4 
Karnofsky Performance Status (KPS) Scale  
Performance Status 
(%) 
Condition 
100 
Normal no complaints; no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self; unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his 
personal needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled; requires special care and assistance. 
30 
Severely disabled; hospital admission is indicated although death not 
imminent. 
20 
Very sick; hospital admission necessary; active supportive treatment 
necessary. 
10 
Moribund; fatal processes progressing rapidly. 
0 
Dead 
 
 

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Appendix 5 
Classification of Graft versus Host Disease (GvHD) 
ACUTE GRAFT VERSUS HOST DISEASE (Przepiorka et al. 1995) 
Severity of Individual Organ Involvement 
Stage 1  maculopapular rash involving less than 25% of the body surface 
Skin 
Stage 2  maculopapular rash involving 25-50% of the body surface 
Stage 3  generalized erythroderma 
Stage 4  generalized erythroderma with bullous formation and often with desquamation 
 
Stage 1  bilirubin 2-3 mg/dL 
Liver 
Stage 2  bilirubin 3-6 mg/dL 
Stage 3  bilirubin 6-15 mg/dL 
Stage 4  bilirubin > 15 mg/dL 
 
Diarrhea is graded Stage 1 to 4 in severity. Nausea and vomiting and/or anorexia caused by 
GvHD is assigned as Stage 1 severity. 
Gut 
The severity of gut involvement is assigned to the most severe involvement noted. Patients 
with visibly bloody diarrhea are at least a Stage 2 gut and grade III overall. 
Stage 1  diarrhea > 500 mL/day in the absence of infectious/medical cause. 
Stage 2  diarrhea > 1000 mL/day 
Stage 3  diarrhea > 1500 mL/day 
Stage 4  severe abdominal pain with or without ileus 
 
Grade 
Grading of acute GvHD 
Skin 
Liver 
Gut 
I 
Stage 1-2 
0 
0 
II 
Stage 3 or 
Stage 1 or 
Stage 1 
III 
- 
Stage 2-3 or 
Stage 2-4 
IV 
Stage 4 or 
Stage 4 
 
 

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CHRONIC GRAFT-VERSUS-HOST DISEASE 
The global scoring system for chronic GvHD (Filipovich et al. 2005)  reflects the clinical 
effect of chronic GvHD on the patient’s functional status. Elements included in this global 
scoring system include both the number of organs or sites involved and the severity within 
each affected organ (note that performance status scoring is not incorporated into the global 
scoring system). The global descriptions of mild, moderate, and severe were chosen to reflect 
the degree of organ impact and functional impairment due to chronic GvHD. Note that the 
global scoring system can be applied only after the diagnosis of chronic GvHD is confirmed 
by either (1) the presence of a diagnostic feature or, if a diagnostic feature is not present, 
(2) at least 1 distinctive manifestation of chronic GvHD with the diagnosis supported by 
histologic, radiologic, or laboratory evidence of GvHD from any site. 
•  Mild chronic GvHD
• 
 involves only 1 or 2 organs or sites (except the lung: see 
below), with no clinically significant functional impairment (maximum of score 1 
in all affected organs or sites).  
Moderate chronic GvHD
• 
 involves (1) at least 1 organ or site with clinically 
significant but no major disability (maximum score of 2 in any affected organ or 
site) or (2) 3 or more organs or sites with no clinically significant functional 
impairment (maximum score of 1 in all affected organs or sites). A lung score of 1 
will also be considered moderate chronic GvHD.  
Severe chronic GvHD
 
 indicates major disability caused by chronic GvHD (score of 
3 in any organ or site). A lung score of 2 or greater will also be considered severe 
chronic GvHD.  
Table 2 shows the scoring system for individual organs. 
Table 2 
Organ scoring of chronic GvHD 
 
SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
PERFORMANCE 
SCORE  
 
KPS, ECOG or LPS 
Asymptomatic and 
fully active (ECOG 
0; KPS or LPS 
100%) 
Symptomatic, fully 
ambulatory, 
restricted only in 
physically 
strenuous activity 
(ECOG 1, KPS or 
LPS 80-90%) 
Symptomatic, 
ambulatory, 
capable of self 
care, >50% of 
waking hours out 
of bed (ECOG 2, 
KPS or LPS 
60-70%) 
Symptomatic, 
limited self-care, 
>50% of waking 
hours in bed 
(ECOG 3-4, KPS 
or LPS <60%) 
SKIN  
Clinical features:  
Maculopapular rash  
Lichen planus-like 
features  
Papulosquamous 
lesions or ichthyosis 
Hyperpigmentation  
Hypopigmentation  
Keratosis pilaris  
No symptoms 
<18% BSA with 
disease signs but 
NO sclerotic 
features 
19-50% BSA OR 
involvement with 
superficial sclerotic 
features “not 
hidebound” (able 
to pinch) 
>50% BSA OR 
deep sclerotic 
features 
“hidebound” 
(unable to pinch) 
OR impaired 
mobility, ulceration 
or severe pruritus 

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SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
Erythema  
Erythroderma  
Poikiloderma  
Sclerotic features  
Pruritus  
Hair involvement 
Nail involvement  
 
% BSA involved 
MOUTH 
No symptoms 
Mild symptoms 
with disease signs 
but not limiting 
oral intake 
significantly 
Moderate 
symptoms with 
disease signs with 
partial limitation of 
oral intake 
Severe symptoms 
with disease signs 
on examination 
with major 
limitation of oral 
intake 
EYES  
 
Mean tear test (mm):  
>10 
 6-10 
 ≤5  
Not done 
No symptoms 
Mild dry eye 
symptoms not 
affecting ADL 
(requiring eye 
drops <3 x per day) 
OR asymptomatic 
signs of 
keratoconjunctivitis 
sicca 
Moderate dry eye 
symptoms partially 
affecting ADL 
(requiring drops > 
3 x per day or 
punctal plugs), 
WITHOUT vision 
impairment 
Severe dry eye 
symptoms 
significantly 
affecting ADL 
(special eyeware to 
relieve pain) OR 
unable to work 
because of ocular 
symptoms OR loss 
of vision caused by 
keratoconjunctivitis 
sicca 
GI TRACT 
No symptoms 
Symptoms such as 
dysphagia, 
anorexia, nausea, 
vomiting, 
abdominal pain or 
diarrhea without 
significant weight 
loss (<5%) 
Symptoms 
associated with 
mild to moderate 
weight loss (5-
15%) 
Symptoms 
associated with 
significant weight 
loss >15%, requires 
nutritional 
supplement for 
most calorie needs 
OR esophageal 
dilation 
LIVER 
Normal LFT 
Elevated Bilirubin, 
AP, AST or ALT 
<2 x ULN 
Bilirubin >3 mg/dL 
or Bilirubin, 
enzymes 2-5 x 
ULN 
Bilirubin or 
enzymes > 5 x 
ULN 
LUNGS†  
 
FEV1  
DLCO 
No symptoms 
FEV1 >80% OR 
LFS=2 
Mild symptoms 
(shortness of breath 
after climbing one 
flight of steps) 
FEV1 60-79% OR 
LFS 3-5 
Moderate 
symptoms 
(shortness of 
breath after 
walking on flat 
ground) FEV1 40-
59% OR LFS 6-9 
Severe symptoms 
(shortness of breath 
at rest; requiring 
O2) FEV1 <39% 
OR LFS 10-12 
JOINTS AND 
FASCIA 
No symptoms 
Mild tightness of 
arms or legs, 
normal or mild 
decreased range of 
motion (ROM) 
Tightness of arms 
or legs OR joint 
contractures, 
erythema thought 
due to fasciitis, 
Contractures 
WITH significant 
decrease of ROM 
AND significant 
limitation of ADL 

ATIR101 
 
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20 November 2015  
 
 
 
 
Confidential 
 
Page 72 of 75 
 
 
SCORE 0 
SCORE 1 
SCORE 2 
SCORE 3 
AND not affecting 
ADL 
moderate decrease 
ROM AND mild to 
moderate limitation 
of ADL 
(unable to tie shoes, 
button shirts, dress 
self etc.) 
GENITAL TRACT 
No symptoms 
Symptomatic with 
mild signs on exam 
AND no effect on 
coitus and minimal 
discomfort with 
gynecologic exam 
Symptomatic with 
moderate signs on 
exam AND with 
mild dyspareunia 
or discomfort with 
gynecologic exam 
Symptomatic 
WITH advanced 
signs (stricture, 
labial agglutination 
or severe 
ulceration) AND 
severe pain with 
coitus or inability 
to insert vaginal 
speculum 
OTHER INDICATORS, CLINICAL MANIFESTATIONS OR COMPLICATIONS RELATED TO 
CHRONIC GvHD  
(check all that apply and assign a score to its severity (0-3) based on its functional impact where applicable 
(none-0, mild-1, moderate-2, severe-3)  
Esophageal stricture or web___  
Pericardial effusion___  
Pleural Effusion(s)___  
Ascites (serositis)___  
Nephrotic syndrome___  
Peripheral neuropathy___  
Myasthenia gravis___  
Cardiomyopathy___  
Eosinophilia > 500μL___  
Polymyositis___  
Cardiac conduction defects___  
Coronary artery involvement___  
Platelets <100,000/μL ___  
Progressive onset___  
Others: specify:___ 
†Pulmonary scoring should be performed using both the symptom and pulmonary function testing (PFT) scale 
whenever possible. When discrepancy exists between pulmonary symptom or PFT scores the higher value 
should be used for final scoring. Scoring using the Lung Function Score (LFS) is preferred, but if DLCO is not 
available, grading using FEV1 should be used. The LFS is a global assessment of lung function after the 
diagnosis of bronchiolitis obliterans has already been established. The percent predicted FEV1 and DLCO 
(adjusted for hematocrit but not alveolar volume) should be converted to a numeric score as follows: >80% = 1; 
70-79% = 2; 60-69% = 3; 50-59% = 4; 40-49% = 5; <40% = 6. The LFS = FEV1 score + DLCO score, with a 
possible range of 2-12. GvHD indicates graft versus host disease; ECOG, Eastern Cooperative Oncology 
Group; KPS, Karnofsky Performance Status; LPS, Lansky Performance Status; BSA, body surface area; ADL, 
activities of daily living; LFTs, liver function tests; AP, alkaline phosphatase; ALT, alanine aminotransferase; 
AST, aspartate aminotransferase; ULN, upper limit of normal. 
 

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Clinical Study Protocol: CR-AIR-008 (after Amendment 1) 
20 November 2015  
 
 
 
 
Confidential 
 
Page 73 of 75 
 
Appendix 6 
Adverse Events Not to Be Reported in the Electronic Case Report Form 
When Occurring Before ATIR101 Infusion 
1. ANTICIPATED AEs DUE TO THE USE OF HEMATOPOIETIC GROWTH 
FACTORS: 
• Fever and muscle or bone pain due to G-CSF 
 
2. ANTICIPATED AEs DUE TO THE CONDITIONING REGIMEN (expected to occur in 
the period between the start of the conditioning regimen and ATIR101 infusion):  
• Neutropenia, leukopenia, and thrombocytopenia 
• Marrow aplasia 
• Fever, chills, allergic reaction, dermatological reactions, increased liver enzymes, 
alopecia, hematuria, gastrointestinal toxicity, and sterility 
• Anaemia 
• Additional acute toxicities including nausea and vomiting, mucositis, diarrhea, 
parotitis, and skin erythema 
• Fatigue and lethargy 
• Hypoproteinaemia, hypoglycaemia, hyperglycaemia 
• Blood electrolytes abnormal 
• Renal impairment 
 

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Clinical Study Protocol: CR-AIR-008 (after Amendment 1) 
20 November 2015  
 
 
 
 
Confidential 
 
Page 75 of 75 
 
Appendix 8 
Investigator’s Signature 
Study Title: 
An exploratory, open-label, multicenter study to evaluate the 
safety and efficacy of a two-dose regimen of ATIR101, a 
T-lymphocyte enriched leukocyte preparation depleted ex vivo 
of host alloreactive T-cells (using photodynamic treatment), in 
patients with a hematologic malignancy, who received a CD34-
selected hematopoietic stem cell transplantation from a 
haploidentical donor 
Study Number: 
CR-AIR-008 
Original Protocol Date: 
9 July 2015 
Amendment 1 Date: 
20 November 2015 
 
I have read all pages of this clinical study protocol for which Kiadis Pharma Netherlands 
B.V. is the sponsor. I agree that it contains all the information required to conduct this study. 
I agree to conduct the study as outlined in the protocol and to comply with all the terms and 
conditions set out therein. I confirm that I will conduct the study in accordance with the ICH 
GCP guidelines and the provisions of the Helsinki Declaration. I will also ensure that all 
relevant members of my staff have access to copies of this protocol, the ICH GCP guidelines 
and the Helsinki Declaration to enable them to work in accordance with the provisions of 
these documents.” 
 
 
 
 
Signed: 
 
 
Date:  
 
 
Printed name: ………………………………………………………………………. 
Address: ……………………………………………………………………………. 
……………………………………………………………………………………… 
………………………………………………………………………………………