A Phase I Single-arm, Open-label Prospective Study to Evaluate the Efficacy and Safety of Peripheral Blood Derived Autologous Multi-lineage Potential Cells (AMPC) in Relapsed/Refractory Acute Myeloid Leukemia (AMPCAL Study)
Phase: PHASE1
Conditions: Acute Myeloid Leukaemia Recurrent
Sponsor: Lai Corporation Pty. Ltd.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase I Study Protocol of Autologous Multi-lineage Potential Cells (AMPC) on Acute Myeloid 
Leukaemia 
 
 
 
 
Date: 22 January 2019 
 
 
Version: 4.1 
 
 
 
 
 
 
 
 

Acute Myeloid Leukemia Treatment with AMPC Private Trial Scope 
Primary Outcome 
Measures 
To determine overall response rate (ORR) of peripheral blood-derived 
Autologous Multi-lineage Potential Cells (AMPC) in refractory or 
relapsed acute myeloid leukemia (AML) at 12 months 
 
Overall response rate (ORR) is defined as whether the patient achieves 
complete remission (CR) or complete remission with incomplete blood 
count recovery (CRi) 
 
CR Requirements: 
• Bone marrow aspiration shows less than 5% of abnormal blasts as 
determined by evidence from flow cytometry or immunohistochemistry 
• Bone marrow biopsy shows no clusters of blast cell 
• Normal values for absolute neutrophil count in peripheral blood exceeds 
1,000/microL 
• Platelet count in peripheral blood exceeds 100,000/microL 
• Absence of extramedullary AML 
 
CRi Requirements: 
• All parameters of CR except platelet recovery or neutrophil recovery 
• Incomplete recovery—platelet count is less than 100,000/microL or 
neutrophil count less than 1,000/microL in peripheral blood 
Secondary 
Outcome 
Measures 
1) To determine safety profile and treatment-related adverse events (AE) 
upto 12-month follow up period 
AE is defined as any unintended or undesirable experience that occur 
during the course of the clinical investigation regardless of whether they 
are considered to be drug-related 
2) ORR at 3 and 6 months 
3) Overall survival (OS) rate at 12 months 
4) Time-to-next treatment (TTNT), defined as the time from the start of 
AMPC therapy to the start date of a subsequent line of therapy. 
Title 
The effects of AMPC in the treatments of refractory or relapsed AML 

Brief Summary 
 
A private trial for evaluating the overall response rate contributed by 
AMPC in AML in refractory or relapsed AML 
Detailed 
Description 
After inclusion and exclusion criteria has been determined and approved, 
written informed consent will be obtained from the candidate. All medical 
history relevant to the diagnosis of AML will be collected. 
Screening period: 
The screening period could extend from 0 to 7 days depending on the 
completion of screening laboratory results as below. 
On day -5 (up to day -1), the patient will undergo a screening test for the 
following test items: 
• BUN, creatinine, electrolyte, liver function test (LFT) 
• Full blood count (FBC), including blood smear 
• Hepatitis B/C 
• Human T lymphocytic virus type I and II (HTLV-I/II) 
• HIV1/2 
• Syphilis serology 
• Mycoplasma serology 
For Hepatitis B/C,HTLV-I/II, HIV1/2, Syphilis serology, and Mycoplasma 
serology, these tests obtained up to 3 months prior to day -5 can be 
allowed for using as screening result. 
• Chest X-ray 
• Bone marrow study including aspiration with wright’s stain, biopsy, 
flow cytometry, and chromosome study (Any molecular testing for AML 
is optional.). 
Bone marrow biopsy can be omitted if the prior study performed within 
14 days before day-5 and the available materials (core biopsy and slides) 
and result can be obtained for pathological review. In this case, only bone 
marrow aspiration for Wright’s stain, flow cytometry, and chromosome 
study will be performed. 
Bone marrow biopsy will be repeated if the previous result has been 
performed more than 14 days prior to day -5 and/or FBC at day -5 reveals 
peripheral blast count higher than 10% of total white blood cells. 

For chromosome study (cytogenetics), the previous result before the 
recent line of chemotherapy prior to enrolment can be used for the 
screening data. 
 
On day 0, peripheral blood will then be collected, ranging from 250mL to 
400mL depending on candidate fitness. The blood is collected into a 
sterile blood bag and sealed. Subsequent processes will be conducted in 
the blood bag within a closed-system to minimize contamination risks. 
FBC will be collected in order to determine the disease status. After that, 
the investigator will consider to prescribe blood transfusion for the 
candidate. 
 
On day 0 to day 3, the collected blood will be sent to the laboratory for 
stem cell culture, and a sample of the collected blood will be sent to a 
third-party laboratory for contamination testing of the following 
parameters: 
• Bacterial endotoxin 
• Total viable aerobic count 
• Total viable count 
• Microbial growth 
• Mycoplasma real-time PCR test 
 
On day 4, the biotest results will be released and the safety profiles of the 
AMPC product must be completed and passed before the cultured stem 
cells may be released for treatment 
 
On day 5, candidates will receive an infusion of the cultured stem cells. 
Prior to the infusion, FBC and blood chemistry (BUN, Cr, electrolyte, 
LFT) will be collected and the treating doctor will first conduct an allergy 
skin test to determine suitability for reinfusion. The cultured stem cells are 
then reinfused intravenously into the candidate in a process that could 
take up to 2 hours 

 
The candidate participation will take place on day 0 to day 1 or 2 (if blood 
transfusion is required) and day 5 (period adjusted for blood transfusion if 
required) for peripheral blood collection and stem cell reinfusion 
respectively; with 12 month follow up after treatment; 
• 3 days post-treatment follow-up: full blood count test and blood 
smear, BUN, Cr, electrolyte, LFT 
•  10 days post-treatment follow-up: full blood count test and blood 
smear, BUN, Cr, electrolyte, LFT 
•  1 month (+/-7 days) post-treatment follow-up: full blood count 
test and blood smear, BUN, Cr, electrolyte, LFT, bone marrow 
study 
•  3 month (+/-7 days) post-treatment follow-up: full blood count 
test and blood smear, BUN, Cr, electrolyte, LFT, bone marrow 
study 
• 6 month (+/-7 days) post-treatment follow-up: full blood count test 
with bone marrow study 
• 12 month (+/-7 days)  post-treatment follow-up: full blood count 
test with bone marrow study 
Study Type 
Interventional 
Study Design 
Single-arm, open label, prospective study 
Condition 
Relapsed/Refractory Acute Myeloid Leukemia 
Intervention 
Multi-lineage potential cells which were induced to de-differentiate from 
somatic leukocytes. Cells are autologous with respect to the patient, and 
are prepared in a suspension and administered via intravenous infusion.  
 
An estimated average of 1 x 108 (0.5 to 5 x 108) cells/per suspension(275 
to 450mL) will be infused into the patient via intravenous infusion on day 
5. Cell counts depend on yield of initial leukocyte harvest on day 0. 
Study Arms 
Experimental: Pilot study 
Sample size: 3 

To determine the effects of AMPC AML by monitoring the ORR and to 
observe in the long-term any manifestation of AE 
 
Experimental: Phase II of private study, which can be started only after 
complete 3 months of AMPC therapy in the first 3 patients in the pilot 
study and the safety profiles has been approved by investigator (and 
sponsor). 
Sample size: 7 
To determine the effects of AMPC on AML by monitoring the ORR and 
to observe in the long-term any manifestation of AE 
Estimated 
Enrolment 
10 
Eligibility Criteria 
Inclusion Criteria: 
• Must be unequivocally diagnosed with AML according to WHO 
classification with accompanying bone marrow biopsy and blood panel 
results 
• Must have refractory AML, defined as disease unresponsive to initial 
treatment; or relapsed AML that re-occured after treatment with 
conventional high dose chemotherapy 
• Candidates who have no available match-sibling donor for bone marrow 
transplantation (BMT) or are not suitable for BMT due to any reason. 
• Must have had prior treatment with chemotherapy at least 30 days prior 
to day 0 of this study and have recovered from treatment-related toxicity 
of chemotherapeutic agents with the exception of persistent diseases 
• Age 20 to 60 years old 
 
Exclusion Criteria: 
• Candidates who received any investigational therapies 4 weeks prior to 
treatment with this protocol 
• Candidates who received radiotherapy within 4 weeks prior to the 
treatment of this protocol 
• Candidates who have not recovered from any AE caused by radiotherapy 

or any agents received 4 weeks earlier 
• Candidates who have had a prior allogeneic stem cell transplant 
• Known case of extramedullary myeloid tumor (myeloid sarcoma) 
• Pregnant or breastfeeding women 
• Hydroxyurea has been prescribed within 10 days prior to day-5 
• Candidates have any abnormal screening laboratory results as below; 
     - Hemoglobin < 9 g/dL 
     - Total white blood cells count > 30,000/microL (without ongoing G-
CSF therapy) 
     - Platelet cound < 75,000/microL 
     - Creatinine clearance < 30 mL/min/1.73 m2 (by Cockcroft and Gault 
formula) 
     - ALT > 5x upper normal limit 
     - Bone marrow study at screening period show blast > 40% of total 
nucleated cells or severe hypocellularity (defined as < 25% of normal 
cellularity for corresponding age) with presence of cluster of blasts 
• Candidates have active heart disease including recent or chronic heart 
failure, unstable angina, recent acute myocardial infarction, or significant 
arrhythmia within 6 months of recruitment. 
• Candidates have concurrent malignancies unless the candidates have 
been free of the disease for at least 5 years. 
• Candidates positive for HIV1/2, hepatitis B/C, HTLVI/II, and 
Syphilis 
Gender 
Male and Female 
Statistical Analysis 
Plan 
Statistical Analysis Overview 
• For this open-label study, baseline characteristics and clinical primary 
and secondary outcomes will be descriptive analysed in order to 
explore the efficacy and treatment safety of AMPC in relapse/refractory 
AML patients who are not suitable for standard therapy. 
• There will be no statistical comparison between results from this phase 
I study and those from historical study as upper limit of total number of 
treatment patient is very low (N=10). Future phase II study might be 

planned after the completion of phase I study in order to further explore 
this novel treatment role in AML. 
Type of Statistical Test: Other (single group) 
 
Clinical Protocol 
The procedures of the study are divided into four main steps: 
1. Patient recruitment 
2. Peripheral blood collection 
3. AMPC product culture and analysis 
4. Autologous reinfusion of product 
 
Patient recruitment 
During patient recruitment, the investigator will inform volunteer of the objectives and procedure 
of the study. In order for a volunteer to be recruited, patient participation must be voluntary and 
volunteer must provide written informed consent to the participation in the study. After consent 
has been given by the patients, the necessary screening laboratory tests must be arranged for each 
patient according to the time frame set in the study design. The test items include: 
 
• BUN, creatinine, electrolyte, liver function test (LFT) 
• Full blood count (FBC), including blood smear 
• Hepatitis B/C 
• Human T lymphocytic virus type I and II (HTLV-I/II) 
• HIV1/2 
• Syphilis serology 
• Mycoplasma serology 
 
For Hepatitis B/C,HTLV-I/II, HIV1/2, Syphilis serology, and Mycoplasma serology, these tests 
obtained up to 3 months prior to day -5 can be allowed for using as screening result. 
 
Bone marrow study including aspiration with wright’s stain, biopsy, flow cytometry, and 
chromosome study (Any molecular testing for AML is optional.). 
 

Bone marrow biopsy can be omitted if the prior study performed within 14 days before day-5 
and the available materials (core biopsy and slides) and result can be obtained for pathological 
review. In this case, only bone marrow aspiration for Wright’s stain, flow cytometry, and 
chromosome study will be performed. 
 
Bone marrow biopsy will be repeated if the previous result has been performed more than 14 
days prior to day -5 and/or FBC at day -5 reveals peripheral blast count higher than 10% of total 
white blood cells. 
 
For chromosome study (cytogenetics), the previous result before the recent line of chemotherapy 
prior to enrolment can be used for the screening data. 
 
The results of all screening testings must be completed before the determination of the eligibility 
for treatment according to inclusion and exclusion criteria. A baseline measurement of the 
outcome measures of the study will also be determined during this step. The volunteers will then 
be appointed for the “day 0” visit in order to inform the eligibility for further study participation 
and peripheral blood collection. 
 
Peripheral blood collection 
Approximately 1 hour prior to blood collection, a temperature-controlled container of between 4 
to 12°C is prepared. A universal identification number (UIN) label prepared for each patient and 
affixed on a 250mL blood bag with 35mL anticoagulant. The UIN must also include the patient's 
name, sex, date of birth, and date of collection. 
 
Once blood collection is complete, the blood bag will be weighed and the weight is recorded. 
The tubes will then be sealed with a tube sealer to ensure minimal contamination from external 
environments. The blood bag will then be placed in the temperature-controlled container while 
ensuring that the temperature of between 4 to 12°C is maintained during transport of the product. 
After blood collection, the volunteers who have symptomatic anemia may be admitted for blood 
transfusion session. 
 
Culture of the investigational product 
All laboratory technicians must check the blood sample upon receipt to ensure it is the correct 

sample viable for processing. A laboratory label with the corresponding UIN must also be affixed 
to the blood sample.  
 
The blood sample will be centrifuged for white blood cells and cultured according to the 
Manufacturing and Quality Aspects of Autologous Multi-lineage Potential Cells provided by 
Autologous Stem Cell Technology Pty Ltd to culture the investigational product. During this 
time, a sample of the product will be retrieved under a biosafety cabinet to be sent for 
contamination testing to ensure safety of the product prior to release. 
 
Product analysis 
The investigational product will also be analyzed prior to release of sample for reinfusion to 
ensure quality of the product. These include white blood cell composition analysis, 
contamination testing, survival rate analysis, and cell surface marker analysis. 
 
Contamination testing: Testing will be conducted by third party laboratories for total viable 
aerobic count, microbial growth, and endotoxin. The test results must reflect the safety of the 
sample prior to sample release to ensure safe administration of the product. 
 
White blood cell composition: The complete blood count (CBC) of the sample must also be 
analyzed to determine the composition of leukocytes within the sample. The results will be 
broken down into monocytes, lymphocytes, and neutrophils. 
 
Viability testing: The viability of leukocytes within the sample will be analyzed via flow 
cytometry with 7-AAD staining and the Trucount Tube to determine the composition of 7-AAD 
negative cells. The sample must reflect more than 60% cell viability. 
 
Cell surface marker analysis: The cell surface markers of the sample population will also be 
determined via flow cytometry. The CD45+ cells and CD34+ cells within the population will be 
calculated with the Trucount Tube.  
 
These tests results must be ready prior to reinfusion. Any logistical arrangements must take this 
into consideration. The comprehensive specifications of the product, including the test methods 

and optimal results for each parameter is documented in the Manufacturing and Quality Aspects 
of Autologous Multilineage Potential Cells document prepared by Autologous Stem Cell 
Technology Pty Ltd. 
 
 
AMPC Product reinfusion 
After the contamination testing that reflects sample safety is received, the sample will be 
released for reinfusion. The sample will be placed in a temperature controlled container of 
between 4 to 12°C and affixed with the correct UIN. 
 
The investigator will confirm that the patient details match the UIN affixed on the sample and 
will then provide a 1mL stem cell allergy test on the patient. If this testing result at 30 minutes 
shows no allergic reaction, stem cell reinfusion will be commenced. 
 
The blood bag containing the sample will first be connected to a blood giving set with a Y pump 
that is also connected to 0.9% sodium chloride solution. A 20 or 22 gauge needle will then be 
intravenously inserted into the patient's vein and a test sample of 5mL 0.9% sodium chloride 
solution infused through the needle to ensure correct needle placement. The connecting tubes 
from the blood giving set will then be connected to the needle and 0.9% sodium chloride solution 
will be infused for 5 minutes before the sample is infused in its entirety. During reinfusion, the 
nurse will maintain records of the duration of reinfusion, any physical changes, body 
temperature, blood pressure, pulse oximetry, and heart rate. 
 
Table of events 
Assessment Screening 
period 
Treatment period 
Post-treatment Follow-up Period (PTFP) 
From Day-5 to 
Day-1 
Day 0 
Day 5 
Day 
3 
Day 
10 
Month 
1 
Month 
3 
Month 
6 
Month 
12