18-457 Manual - Laboratory PDF

(i)
Central Laboratory Manual

United States
Protocol Title:
A Phase 1b/2a open-label, multi-center study to assess the safety,

efficacy and pharmacokinetics of intrapatient dose-adjusted
brequinar and inhibition of dihydroorotate dehydrogenase (DHODH)
in adult subjects with acute myelogenous leukemia (AML)
Prepared for: Prepared by:
Clear Creek Bio, Inc. LabConnect, LLC

CCB-01 CLEACB01
PSG-FRM-002A.05 Central Laboratory Manual LabConnect, LLC

CONTACT INFORMATION
LABCONNECT, LLC CONTACTS

LabConnect Customer Service
2304 Silverdale Dr., Suite 100
Johnson City, TN 37601
P: 1-800-501-7947
customerservice@labconnectllc.com
www.labconnectllc.com
Falecia Kindle
Manager, Project Support Services
2304 Silverdale Dr., Suite 100
Johnson City, TN 37601
423-794-3754 P
fkindle@labconnectllc.com
SPONSOR CONTACTS
Barbara Powers, MSN, Ph.D. Daniel C. Ferrone

Clinical Operations Project Manager
Clear Creek Bio, Inc. Novella Clinical
585 Massachusetts Avenue, 4th Floor 1700 Perimeter Park Drive
Cambridge MA 02139 Morrisville, NC 27560
484-686-0545 p 919-972-7158 p
bpowers@clearcreekbio.com dferrone@novellaclinical.com
CLEACB01 North America Lab Manual CCB-01

02-Oct-2018 Page 2 of 24 Final V1.0
SCHEDULES AND SHIPPING
LabConnect Customer Service Hours:
+1-800-501-7947
Monday - Friday 08:30-20:00 EST
Saturday 09:00-14:00 EST
Detailed instructions on packaging and shipping specimens are provided in Section 5.
Holidays
Holidays will affect the delivery of specimens on these days.
Please DO NOT ship specimens on or the day before holidays listed below.
US Holidays 2018 2019 2020

Day Date Day Date Day Date
New Year’s Day Mon Jan 1 Tue Jan 1 Wed Jan 1
Memorial Day Mon May 28 Mon May 27 Mon May 25
Independence Day Wed Jul 4 Thurs Jul 4 Sat Jul 4
Labor Day Mon Sep 3 Mon Sep 2 Mon Sep 7
Thanksgiving Thurs Nov 22 Thurs Nov 28 Thurs Nov 26
Christmas Day Tue Dec 25 Wed Dec 25 Fri Dec 25
NOTE:
Locally observed holidays may disrupt courier service within your area. Please call your courier
in advance for local pickup schedules.

TABLE OF CONTENTS
Contact Information ..................................................................................................... 2

LabConnect, LLC Contacts .......................................................................................... 2
Sponsor Contacts ...................................................................................................... 2
Schedules and Shipping................................................................................................ 3
SECTION 1: Clinical Trial Materials ................................................................................. 5
Clinical Trial Supplies................................................................................................. 5
Ordering Additional Supplies ...................................................................................... 5
SECTION 2: LabConnect Event Schedule ........................................................................ 7
SECTION 3: Requisitions and Study Specific Forms .......................................................... 8
About The Requisition................................................................................................ 8
Query Process .......................................................................................................... 8
Completed Requisition ............................................................................................... 8
SECTION 4: Specimen Collection and Preparation .......................................................... 11
Venipuncture Collection Procedures ........................................................................... 11
Recommended Order of Draw For Multiple Specimen Collection .................................... 12
Specimen Collection Table........................................................................................ 13
Specimen Collection and Preparation Procedures ........................................................ 14
SECTION 5: Shipment Preparations ............................................................................. 15
Pre-Addressed FedEx Express Airbills: US Sites .......................................................... 15
Shipping Schedule .................................................................................................. 16
Shipping Materials .................................................................................................. 17
Packaging Specimens into the Insulated-Ambient Shipper ............................................ 18
Packaging Specimens into the Frozen Shipper ............................................................ 20
SECTION 6: Lab Testing and Reporting Policies ............................................................. 21
Test Cancellations ................................................................................................... 21
Appendices ............................................................................................................... 22
Sponsor Approval ...................................................................................................... 24

SECTION 1: CLINICAL TRIAL MATERIALS
CLINICAL TRIAL SUPPLIES
To ensure efficient and convenient collection and shipment of laboratory specimens throughout
the clinical trial, LabConnect will provide the investigative sites with the following kits:
Visit Kit Name Kit Shipper Type(s)

Cycle 1 Day 1 Predose
Cycle 1 Day 1 1Hr Postdose
Cycle 1 Day 1 2Hr Postdose Cycle 1 Day 1 PK Kit Bagged Kit
Cycle 1 Day 8 Predose Cycle 1 Day 8 PK Kit Bagged Kit
Final Visit Final Visit PK Kit Bagged Kit
Unscheduled Unscheduled PK Kit Bagged Kit
Cycle 1 Day 1 Predose
Cycle 1 Day 2 24Hr Postdose Flow Cytometry Kit Mini-Ambient
Screening
Cycle 2 Day 8
Day 43 Bone Marrow Collection Kit Mini-Ambient
Final Visit
Unscheduled
Each kit will be labeled with the appropriate visit name and should be used for the specific visit
indicated on the box label. Each kit will include the applicable specimen collection tubes,
laboratory requisition forms, transfer pipettes, gel wraps, absorbent wraps, pressure bag, and
any other necessary supplies for the visit collection.
Kits are supplied in the shipment containers that are to be used for shipping specimens to
LabConnect (see Section 5) and labeled with the pre-addressed return airbills.
EXTRA SUPPLIES
In addition to the visit specific kits, LabConnect will provide investigative sites with the
following:
· Central Laboratory Manual
· Extra Supply Kit (includes phlebotomy supplies, blood collection tubes, shipping
materials, and parafilm)
ORDERING ADDITIONAL SUPPLIES

Additional laboratory collection kits may be ordered by:
· Calling Clinical Trial Materials at +1 800-501-7947 ext. 2
· Scanning and Emailing a Supply Reorder Form to Workorders@labconnectllc.com
· Faxing a Supply Reorder Form to Customer Service at +1 423-722-3166
Note: Supply Reorder Form is located in Appendix A.
Allow 7-10 business days for delivery of supplies. For expedited shipments call Clinical Trial
Materials at 1-800-501-7947 ext 2 (additional fees apply for expedited shipments).

IMPORTANT REMINDERS
· Always use the correct kit for the visit being completed.
· Check the expiration date of the kit before use. If expired kits are used, tests may be
canceled by the laboratory. The expiration date can be found on the kit box.
· It is the responsibility of the investigative sites to rotate laboratory supplies and use kits
prior to their expiration dates.
AT STUDY TERMINATION, PLEASE DISCARD ALL SUPPLIES RELATED TO THIS

PROTOCOL. DO NOT RETURN SUPPLIES TO LABCONNECT.

SECTION 2: LABCONNECT EVENT SCHEDULE
Screen Cycle 1 (Study Days 1 – Dose Maintenance Final F/U Survival

b
14) Adjustment Dose Cycle Visit Phone
Cycle (Cycle 2 (no dose Call
CCB-01 Schedule of Events and beyond as adjustment)
needed) Every 2
weeks
D1 D2 D3 D4 D8 D1 D8 D1 Final
Visit
+2
Proceduresa wks
Flow Cytometryf X X X
Bone Marrow Samplingh X X X
X X X X X X X X X
Brequinar/DHO Plasma Samplei
X X X X
Biobanking samplesj
a. Visit window of ± 1 day for dose escalation cycles; window of ± 3 days for non dose escalation cycles.
f. Flow cytometry testing of peripheral blood is to be obtained at 0 (pre-dose C1D1), post dose 24 and 48hours..
g. Testing panel is per institutional standard of care; obtain sample at Screening.
h. Bone marrow sampling local testing will include analysis of the aspirate on smear, core biopsy by microscopy, flow cytometry, and karyotype for
cytogenetics. Local molecular analysis will be performed on the screening bone marrow samples only. All bone marrow samples will be sent for biobanking
from where further analysis can be done. Perform bone marrow sampling at screening, at study Day 22 (C2D8) with a window ±7 days, at Day 43, and once
every 12 weeks after a stable dose has been reached. Timing of this procedure may be adjusted to ensure results are available for the next clinic visit.
i. Brequinar/DHO plasma sampling schedule: Cycle 1: 0 (pre-dose), post dose 1, 2, 4, 6, 24, 48, 72 hours and C1D8 pre-dose (+84h after C1D4 dose); Cycle 2
and adjustment cycles: pre-dose Days 1 and 8; every 2-week Maintenance Cycle until 3-months on drug: pre-dose Day 1 and every 2 to 4 week Maintenance
Dose Cycle beyond 3-months on drug. Day 1 sample window ±15 minutes through 6h draw; window for additional C1 draws ±2h; window for Cycle 2 and
beyond plasma brequinar/DHO draws ±4h. Ensure trough samples (e.g., C1D1, C2D1, C3D1) are obtained prior to dosing. Plasma samples for
brequinar/DHO for expansion cohort are to be obtained prior to dosing on Day 1 of each 2-week cycle for the first 3 cycles, then every 12 weeks.
j. Biobanking samples (bone marrow) are to be collected whenever bone marrow sampling is performed.

SECTION 3: REQUISITIONS AND STUDY SPECIFIC FORMS
ABOUT THE REQUISITION

The requisition is a 3-part carbonless form. The requisition contains the same unique 8-digit
identifier as the specimen labels. When writing on the form, align all pages properly and press
firmly with a ballpoint pen. The Subject ID number should be handwritten on the bar coded
labels as the samples are prepared for submission.
Information on the Requisition:

Complete all the fields on the form. Failure to do so will delay results. The information must be
recorded completely, accurately, and legibly. Demographic information should remain
consistent for each subject.
For All Visits:

Please remember to use the proper format when recording the subject ID number. For this
study, this is an 5 digit subject ID number (e.g. XX-YYY). Please ensure that this
information is recorded on the requisition as well as the tubes submitted. If any requisition is
returned incomplete, or if information missing or inconsistent, Customer Service will contact
the investigator site for clarification.
QUERY PROCESS
If there is incomplete or incorrect information on a received requisition, LabConnect will contact
the site for clarification. Customer Service will call the site to clarify any information that is in
doubt. If the site cannot be reached, a message will be left on the voicemail. In addition, an e-
mail will be sent to the study coordinator. If a response is not received, a follow-up email will
be sent the next morning. If a response is not received within three days, the query will be
escalated to the Project Manager or designee to contact the Sponsor/CRO for resolution.
Situations that may prompt a query from LabConnect include, but are not limited to:
ü demographic section left blank on the requisition
ü inconsistent data on requisition from other visits
ü illegible writing on requisition
ü confirmation of long past-stability collection dates
ü missing samples
ü visit type not clear if wrong kit used
ü mis-labeled specimens
If you have questions concerning a query, please contact Customer Service, 1-800-501-7947
ext 3 or customerservice@labconnectllc.com.
COMPLETED REQUISITION
The original (White) copy of the completed requisition accompanies all specimens submitted to
the testing lab. Where applicable, the yellow copy should be submitted with secondary
shipments. The pink copy, and yellow copy where applicable, is retained in your study file
and/or the subject’s medical records.

Standard Requisition: is used when samples are collected at a single collection date and
time. Where applicable, please select the appropriate subject visit from the list provided.
Complete all subject demographics.
Enter the visit collection date

and time.
Indicate visit collected.
If a specimen is not collected, indicate

so by marking the box next to No.
The reasons can be recorded in the
Site Comments section of the form.

Multi-Requisition: The multi-requisition allows you to collect multiple specimens with
different dates/times. Where applicable, please select the appropriate subject visit from the list
provided.
Complete all subject demographics.
If a specimen is not collected, indicate

Enter the specimen collection so by marking the box next to No.
date and time. The reasons can be recorded in the
Site Comments section of the form.

SECTION 4: SPECIMEN COLLECTION AND PREPARATION
NOTE: At least 10 days before any collection procedures, please check expiration dates
on all laboratory supplies. If supplies are past the expiration date, please re-order additional
supplies using the supply reorder form immediately. The earliest expiration date for lab kits can
be found on the lab kit box.
2689577883326895778833
12345678
Clear Creek Bio, Inc.

CCB-01
Cycle 1 Day 1 PK Kit
Expiration Date: 30-Dec-2020
VENIPUNCTURE COLLECTION PROCEDURES
General:
To ensure the accuracy of test results, careful consideration of collection technique and sample
preparation is required. Specimen requirements for each test are listed in this section.
Specimen volume requirements must be adhered to. ALL specimens received must be properly
labeled with the identifying label and subject identifier. The laboratory cannot perform testing
on unlabeled specimens. If you have additional questions or concerns regarding sample
collection and handling, please contact Customer Service at 1-800-501-7947.
Venipuncture:
The following is intended to serve as a guideline for experienced phlebotomists performing
routine venipuncture. Special collection considerations might require an alternate guideline.
Supplies provided for routine venipuncture include needles, syringes or vacutainer holders,
collection tubes, tourniquet, alcohol wipes, gauze, and adhesive strips. The pre-labeled
collection vials are found within each kit. Extra collection and transport tubes and containers
are provided in the extra supply kits provided by LabConnect.
1. Select venipuncture site.

2. Assemble supplies within easy reach of your subject. Put on gloves.
3. Apply tourniquet.
4. Cleanse the site with an alcohol prep pad. Allow the alcohol to air dry.
5. Puncture the vein with needle (there should not be more than two attempts for a
venipuncture), and obtain the tubes needed. The tourniquet should be removed at the
first sign of blood flow to prevent stasis at the puncture site.
NOTE: Maintain the patient’s arm in a downward position to avoid backflow.
6. Remove the needle from the vein, immediately applying pressure to the site.
7. Mix any tubes containing additives (e.g. anticoagulant) thoroughly immediately after
filling to ensure the performance of the tube additive.
8. Check the puncture site to verify bleeding has stopped and apply adhesive strip.
9. Immediately record the subject’s identifier (Subject ID number) on the labels using a
ballpoint pen.

10. Do not recap needle, but dispose of it using the appropriate biohazard needle disposal
unit.
11. Remove gloves and wash hands.
Labeling Specimen Collection Tubes and Transport Vials

The blood collection tubes and transport tubes provided in the visit-specific collection kits are
pre-labeled and require only the subject identifier (Subject ID) to be added using a ballpoint
pen. However, if a blood collection tube or transport vial is defective or is missing; utilize the
extra supplies provided in the Extra Supply Kit.
LabConnect accession (requisition) number.
8-digit barcode
43101234
Sample type
PK
Kit name
CCB-01
SID: Protocol Number
Record the subject’s identifier (SID) on each

specimen label using a black ballpoint pen.
NOTE: The 8-digit barcoded accession number on the specimen label MUST match the 8-digit
barcoded accession number listed on the requisition.
If you are using tubes from the extra supply kit, please write the accession number on the tube
based on the visit requisition form.
RECOMMENDED ORDER OF DRAW FOR MULTIPLE SPECIMEN COLLECTION
Follow the recommended order of draw to prevent cross contamination of additives when
collecting multiple specimens.
Comments
Closure Color Collection Tube Mix by Inverting
EDTA Tube 8 – 10 times Lavender Top
A full inversion is when

the air bubble moves from
one end of the tube to the
other

SPECIMEN COLLECTION TABLE
SHIP *Result
TEST COLLECT PREPARE CONTAINER LABEL STABILITY
TEMP TAT
2 x 2 mL polypropylene
1 x 4 mL Lavender K2EDTA cryovials Primary Tube:
invert gently,
PK
DHO/BRQ centrifuge, Frozen NA NA
Secondary Tube:
transfer equally
PK A, PK B
1 x 4 mL Lavender K2EDTA Primary Tube:

None – transport primary FLOW
Flow Cytometry invert gently Ambient NA NA
collection vial Secondary Tube:
FLOW

BMMC Preparation None – transport primary Bone Marrow
invert gently Ambient 24 hours*** 36 hours
for LabConnect collection vial Secondary Tube:
N/A

Bone Marrow-
BMMC Preparation None – transport primary
invert gently Local NA NA
for Local Lab collection vial
Secondary Tube:
N/A
*Result turnaround time is in business days from receipt at testing laboratory.

*** LabConnect will still process samples if received >24 hours past collection. LabConnect will make a note of this. (Samples will be
shipped day after collection, past the 24 hour stability)

SPECIMEN COLLECTION AND PREPARATION PROCEDURES
Lavender Top K3EDTA Tube Bone Marrow Aspirate (BMMC)

1. Collect bone marrow aspirate per institutional guidelines.
2. Place up to 5mL bone marrow aspirate into the 6mL K3EDTA tube labeled Bone Marrow (minimum
volume for this sample is 1mL).
3. Place remaining bone marrow aspirate into the 6mL K2EDTA tube labeled Bone Marrow-Local.
4. Mix immediately by gently inverting the tube 8-10 times.
5. Record the subject ID number on the specimen labels.
6. Place K3EDTA tube labeled Bone Marrow into sleeve of absorbent wrap for Ambient transport to
LabConnect.
NOTE: K2EDTA tube labeled Bone Marrow-Local is sent to local laboratory. DO NOT ship this sample to
LabConnect
7. See Section 5. Shipment Preparations for shipping schedule of Bone Marrow sample to LabConnect.
Lavender Top K2EDTA Tube (PK Collection)

1. Collect all blood samples in 4mL tube labeled PK.
2. Immediately after filling each collection tube, gently invert it 5 times to thoroughly mix the blood with
the anticoagulant.
3. Place the tube on wet ice until centrifuged.
4. Centrifuge at 1,500 g at 4°C for 10 min within 30 minutes of collection.
5. Use a disposable pipette to transfer equal volumes of the plasma, removed without disturbing the blood
cells, into two 2.0 mL self-standing polypropylene cryogenic storage vials with external threads for the
Primary (PK A) and Backup (PK B) aliquots.
6. Record the subject ID number on the specimen label.
7. Wrap the label with scotch tape to prevent the label from detaching from the vial when stored frozen.
8. Immediately place the cryovials in crushed dry ice until transferred to Cryobox kept in an ultralow
temperature freezer (-80°C) for storage until Frozen shipment.
9. See Section 5. Shipment Preparations for shipping schedule.
Lavender Top K2EDTA Tube (Flow Cytometry)

1. Collect blood samples for immunphenotyping for flow cytometry in 4mL tube labeled Flow Cytometry.
2. Immediately after filling each collection tube, gently invert the tube 5 times to thoroughly mix the blood
with the anticoagulant.
3. Maintain the blood sample at room temperature; do not place on ice, chill or freeze.
4. Record the subject ID number on the specimen label.
5. Place the purple-top Vacutainer tube in a larger protective BD Falcon 50 mL Conical Centrifuge Tube.
6. See Section 5. Shipment Preparations for shipping schedule.

SECTION 5: SHIPMENT PREPARATIONS
Each visit-specific kit has a pre-addressed airbill, attached to the outside of the cardboard shipping
container (see examples below).
· Record the FedEx Tracking Number from the top of each airbill for your records and shipment
tracking purposes.
· Additional airbills can be ordered from LabConnect, but must be ordered prior to the subject visit.
Allow 7-10 business days for delivery of airbills.
PRE-ADDRESSED FEDEX EXPRESS AIRBILLS: US SITES
SHIPMENTS MONDAY THROUGH FRIDAY for

ARRIVALS ON TUESDAY THROUGH SATURDAY
Tracking Number
The top portion of the return
airbill with the tracking number
can be found inside each
collection kit and is provided for
specimen tracking.

SHIPPING SCHEDULE
PK Samples
· For Cycle 1, the Primary (PK A) aliquot of each of the plasma samples must be shipped for next
day delivery on Day 8 as soon as the Day 8 pre-dose sample has been collected and processed.
· For subsequent cycles, process and ship on the last day of collection for any cycle.
· The Backup (PK B) aliquot of each sample should be shipped separately to the analytical
laboratory every month after receiving confirmation the Primary aliquots (vial A) have been
received.
· The transport vials should be placed in a Cryobox. Place the Cryobox in a specimen transport bag
containing the box of samples on top of at least 4 inches of dry ice in a Frozen shipper. Cover the
specimen transport bag with an at least 4 inches of additional dry ice such that the container is
completely filled with dry ice. Attach the cover to the styrofoam container and place it within a
tight-fitting cardboard shipping box.
· Send the package on a Monday-Thursday (never ship on a Friday) for next day delivery by 10:00
a.m. to:
Pyxant Labs Inc.

4720 Forge Road, Suite 108
Colorado Springs, CO 80907
Phone: +1 (719) 593-1165
email: mvann@pyxant.com
· Scan the shipping label and send to notify Pyxant Labs Inc. of the incoming shipment at
mvann@pyxant.com Specify:
- Institution, protocol number (CCB-01), courier, and the tracking number.
- Attach a shipping manifest to the email that lists the following information for each
transport vial contained in the package: protocol number, subject identification number,
subject initials, brequinar dose (mg), sample collection scheduled time and actual time,
sample collection date, and aliquot (A or B).
- Include a scanned copy of the shipping label.
· Note the following holidays, do not ship if sample will arrive on a holiday: January 1 (New Year’s
Day), President’s Day, Memorial Day, Independence Day, Labor Day, Columbus Day, Thanksgiving
Day, Christmas day.
If help is needed, contact Pyxant Labs Inc. mvann@pyxant.com (+1 (719) 593-1165) or Novella project
manager dferrone@Novella.com (919-972-7158)

Flow Cytometry Samples
Samples should be shipped for next day delivery on the day of collection or the next permitted shipping
day, if necessary. Samples should never be shipped on a Friday as the flow cytometry laboratory is
not staffed on weekends.
Send the package on a Monday-Thursday for next day delivery by 10:00 a.m. to:
D. Dombkowski & S. Mordecai

Massachusetts General Hospital
Simches Research Building
CPZN - Room 3.434
185 Cambridge Street
Boston, MA 02114
Phone: 617-726-1683
Scan the shipping label and send as notification of the shipment by email to:
DOMBKOWSKI@HELIX.MGH.HARVARD.EDU
SMORDECAI@mgh.harvard.edu
fpreffer@partners.org
Please specify the name of the originating institution, protocol number CCB-01, the courier, and the
tracking information of the package.
Bone Marrow Samples
Sample going to LabConnect:

K3EDTA Bone Marrow should be shipped the following day after collection to LabConnect for processing.
This should be shipped in an Insulated Ambient shipper. Samples should be shipped Monday through
Thursday. These samples will be sent with an overnight airway bill.
Please complete the Notification of Shipment Form To LabConnect and email to:
pbmc@labconnectllc.com
SHIPPING MATERIALS
Shipping materials for temperature protection are provided in each shipper. For information on
how to package the shipper(s), see following pages.

PACKAGING SPECIMENS INTO THE INSULATED-AMBIENT SHIPPER
FLOW CYTOMETRY SAMPLES WILL BE SENT TO MGH DAY OF COLLECTION.
BONE MARROW SAMPLES WILL BE SENT TO LABCONNECT THE DAY AFTER

COLLECTION.
MAKE CERTAIN ALL SCREW TOP TUBES ARE PROPERLY THREADED AND TOPS ARE
WRAPPED WITH PARAFILM TO PREVENT LEAKAGE.
1. Place collected and prepared primary specimen container(s) into cells of absorbent tube
wrap – only one container per cell. Insert the specimen containers so that they are
standing upright.
2. Roll up the filled absorbent tube wrap and place in 95 kPA pressure bag.
3. Place the gel wrap around the tube filled 95 kPa pressure bag.
4. Place the pressure bag containing all samples in the insulated ambient shipping
container.
5. Quarter fold the white original of the completed visit requisition and place between the
gel wrap and the cardboard shipper.
6. Replace the foam lid on the insulated container.
7. Close the remaining flap of shippers.
8. Ensure the pre-printed air bill is attached to the side of the shipper.
9. Contact FedEx for pickup 1-800-463-3339, fedex.com.

*Notification of Shipment Form To LabConnect
Clear Creek Bio, Inc.

Protocol: CCB-01
Please complete and email this notification form along with a copy of the
REQUISTION to LABCONNECT prior to shipping BBMC samples. (Mon-Thurs)
This will ensure LabConnect is prepared to process the specimens upon receipt within the
required timeframes.
EMAIL TO: pbmc@labconnectllc.com

SAMPLE SHIPMENT DESTINATION:
LABCONNECT, LLC
2304 SILVERDALE DR.
SUITE 100
JOHNSON CITY, TN 37601
DATE OF SHIPMENT: ____ / ____ / _____

mon day year
COURIER USED: FEDEX
AIRBILL NUMBER: __________________________________
SITE NUMBER & NAME OF PERSON PREPARING SHIPMENT: _____________________________
PHONE NUMBER OF PERSON PREPARING SHIPMENT: ____________________________
NUMBER OF SUBJECTS (SAMPLES) INCLUDED IN THIS SHIPMENT: ____________________
SUBJECT ID(S) INCLUDED IN THIS SHIPMENT: ____________________
SAMPLE TYPE: BBMC (K3EDTA)
REQUISITION INCLUDED IN EMAIL TO LABCONNECT: [ ] YES [ ]NO

PACKAGING SPECIMENS INTO THE FROZEN SHIPPER
When packing the frozen shipper ensure the instructions below are followed and
that there is sufficient layering of dry ice both under and on top of the frozen
specimens, such that the specimens are ‘sandwiched’ between the dry ice.
THE FROZEN SHIPPER CONTAINS:

· INSULATED FOAM CONTAINER
· PRE-PRINTED, PRE-ATTACHED AIRBILL
· SPECIMEN TRANSPORT BAG
· ABSORBENT WRAPS
1. Place specimens in the absorbent wrap(s). Ensure that the screw cap lids on the
polypropylene tubes are firmly in place and threaded properly. Dry ice may cause the
lids to loosen while in transit.
2. Place the absorbent wrap(s) or Cryobox into the specimen transport bag, and seal bag
closed.
3. Using insulated gloves, scatter a small amount of dry ice into the bottom of the shipper.
4. Fold and place the transport bag containing frozen samples on top of the layer of dry
ice.
5. Fill the remaining portion of the cooler with dry ice, completely covering the transport
bag and bottom layer of dry ice.
The amount of dry ice is critical to maintain constant temperature within the
shipper during transport.
6. Replace the foam lid on the insulated container.
7. Place the completed white copy of the corresponding requisition(s) on top of the foam
lid.
8. Secure the flaps of the shipper and tape the box closed.
9. Ensure the pre-printed air bill is attached to the top of the shipper.
10. Contact FedEx for pickup 1-800-463-3339, fedex.com.

SECTION 6: LAB TESTING AND REPORTING POLICIES
Additional Testing:
Additional testing is allowed for this protocol. Contact Barbara Powers at
bpowers@clearcreekbio.com for approval.
Retesting:
Retesting is a repeat of a panel or test associated with a scheduled visit. Retesting is NOT
allowed for this protocol.
Unscheduled Testing:
Unscheduled testing occurs when a subject completes a visit at a time, which is not on the
regular event schedule. Unscheduled testing is allowed for this protocol. Sponsor authorization
is required for Unscheduled testing. Contact Barbara Powers at 484-686-0545 for approval. An
option for selecting an Unscheduled visit will be available on Flow Cytometry and Bone Marrow
Collection Kits. For PK samples, Maintenance dose cycles will use an Unscheduled PK requisition
for collection.
Repeat Testing:
LabConnect will provide repeat analysis on specimens previously received at the laboratory
provided the elapsed time does not exceed the stability limits and the quantity of specimen is
sufficient. If you have questions concerning test stability please contact LabConnect Customer
Service, 1-800-501-7947 ext. 5.
TEST CANCELLATIONS
For subject safety reasons, tests may be cancelled if:
· samples are received at an incorrect temperature
· if there is not enough sample to test
· samples are received out of stability
· no sample is submitted to test
· samples not properly labeled

APPENDICES
Appendix A: LabConnect Supply Reorder Form
Complete Form and email: Workorders@labconnectllc.com or Fax: 423-722-3166

Sponsor: Clear Creek Bio, Inc.
Protocol: CCB-01 LC #: CLEACB01
ATTENTION: Allow 7-10 business days for delivery.

Expedited shipments may be accommodated but will incur additional fees.
Call LabConnect Clinical Trial Materials for expedited shipments: 1-800-501-7947 ext 2.
Site Number ________________________ Date Ordered:_____________

Investigator’s Name ________________________ Date Needed:_______________
Requested by ________________________
Telephone Number ________________________
Collection Kits # Required

Flow Cytometry Kit
Bone Marrow Collection Kit
Unscheduled PK Kit
Final Visit PK Kit
NOTE: ALL resupply requests must be approved by the LabConnect/Novella Project Manager
Extra Supplies Qty Extra Supplies Qty

2mL Cryoboxes Scotch tape (roll)
Urine Pregnancy Kits
Frozen Shippers (for PK samples)
4 mL K2EDTA
2 mL polypropylene cryovials
6 mL K3EDTA
6 mL K2EDTA
Other: Other:
NOTE: ALL resupply requests must be approved by the LabConnect/Novella Project

Manager
LABCONNECT USE ONLY

Expiration Date: Order #: QC’d Order Receipt date/time:
Processed by: Date: Ship Date:

Appendix B: Nomogram for Converting RCF to RPM
1) Measure the rotating radius of the centrifuge head – the distance from the center of the rotor to
the bottom of the centrifuge bucket.
2) Using a straight-edged ruler, line up the known rotating radius on the left with the known RPM on
the right.
3) Read the RCF value where the line crosses the graph in the center.
Conversely, RPM can be determined if the RCF value is known using the same nomogram.

SPONSOR APPROVAL
Sponsor Approval Of Study Specific Central Laboratory Manual
VERSION: Final V1.0
SPONSOR: Clear Creek Bio, Inc.
CLIENT: Clear Creek Bio, Inc.
PROTOCOL: CCB-01
This document represents final approval authorizing LabConnect to activate Study. Any
amendments to the said Laboratory Manual require additional written authorizations as such
amendments affect the laboratory operations.
The contents of said material accurately reflect the parameters and requirements of our
Protocol and meet my approval.
Approved by:
Digitally signed by Barbara L. Powers, MSN, PhD
DN: cn=Barbara L. Powers, MSN, PhD, o=Clear Creek Bio, Inc., ou=Clinical Operations, email=bpowers@clearcreekbio.com,
c=US
Date: 2018.10.02 13:45:39 -04'00'
Name (Print) Signature Date
Revision History
Version Date Description of Revision
Final V1.0 02-Oct-2018


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Central Laboratory Manual

A Phase 1b/2a open-label, multi-center study to assess the safety,

Prepared for: Prepared by:

Clear Creek Bio, Inc. LabConnect, LLC

PSG-FRM-002A.05 Central Laboratory Manual LabConnect, LLC

LABCONNECT, LLC CONTACTS

Barbara Powers, MSN, Ph.D. Daniel C. Ferrone

CLEACB01 North America Lab Manual CCB-01

Detailed instructions on packaging and shipping specimens are provided in Section 5.

US Holidays 2018 2019 2020

CLEACB01 North America Lab Manual CCB-01

Contact Information ..................................................................................................... 2

CLEACB01 North America Lab Manual CCB-01

Visit Kit Name Kit Shipper Type(s)

ORDERING ADDITIONAL SUPPLIES

CLEACB01 North America Lab Manual CCB-01

AT STUDY TERMINATION, PLEASE DISCARD ALL SUPPLIES RELATED TO THIS

CLEACB01 North America Lab Manual CCB-01

Screen Cycle 1 (Study Days 1 – Dose Maintenance Final F/U Survival

Bone Marrow Samplingh X X X

CLEACB01 North America Lab Manual CCB-01

ABOUT THE REQUISITION

Information on the Requisition:

For All Visits:

CLEACB01 North America Lab Manual CCB-01

Complete all subject demographics.

Enter the visit collection date

Indicate visit collected.

If a specimen is not collected, indicate

CLEACB01 North America Lab Manual CCB-01

Complete all subject demographics.

If a specimen is not collected, indicate

CLEACB01 North America Lab Manual CCB-01

Clear Creek Bio, Inc.

Expiration Date: 30-Dec-2020

VENIPUNCTURE COLLECTION PROCEDURES

1. Select venipuncture site.

CLEACB01 North America Lab Manual CCB-01

Labeling Specimen Collection Tubes and Transport Vials

Record the subject’s identifier (SID) on each

RECOMMENDED ORDER OF DRAW FOR MULTIPLE SPECIMEN COLLECTION

EDTA Tube 8 – 10 times Lavender Top

A full inversion is when

CLEACB01 North America Lab Manual CCB-01

1 x 4 mL Lavender K2EDTA Primary Tube:

1 x 6 mL Lavender K3EDTA Primary Tube:

1 x 6 mL Lavender K2EDTA Primary Tube:

*Result turnaround time is in business days from receipt at testing laboratory.

CLEACB01 North America Lab Manual CCB-01

Lavender Top K3EDTA Tube Bone Marrow Aspirate (BMMC)

Lavender Top K2EDTA Tube (PK Collection)

Lavender Top K2EDTA Tube (Flow Cytometry)

CLEACB01 North America Lab Manual CCB-01

PRE-ADDRESSED FEDEX EXPRESS AIRBILLS: US SITES

SHIPMENTS MONDAY THROUGH FRIDAY for

CLEACB01 North America Lab Manual CCB-01

Pyxant Labs Inc.

CLEACB01 North America Lab Manual CCB-01

D. Dombkowski & S. Mordecai

Bone Marrow Samples

Sample going to LabConnect:

CLEACB01 North America Lab Manual CCB-01

DATE OF SHIPMENT: / / _

Site Number ____________ Date Ordered:_