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DFCI Protocol 11-001

Randomized Comparison of Intravenous Calaspargase Pegol (SC-PEG asparaginase) and Intravenous Oncaspar®

in Children and Adolescents with Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Pharmacy Manual

Version 2: February 11, 2013

CONFIDENTIAL

DFCI Protocol 11-001 Pharmacy Manual Table of Contents CONFIDENTIAL

Version: V02 Page 1 February 11, 2013


Pharmacy Manual

Table of Contents

Section Title

1. Study Personnel Contact List

2. Protocol and Amendments

3. Investigational Products EZN-2285/Oncaspar®

3.1 Description 3.2 Supply 3.3 Packaging and Labeling 3.4 Storage 3.5 Temperature Excursions 3.6 Investigational Product Stability Reports

4. Pharmacy Procedures

4.1 Investigational Product Receipt 4.2 Investigational Product Accountability 4.3 Randomization and Assignment to Treatment 4.4 Investigational Product Dispensing 4.5 Dose Preparation 4.5.1 EZN-2285 4.5.2 Oncaspar® 4.6 Dose Administration 4.6.1 EZN-2285 4.6.2 Oncaspar® 4.7 Investigational Product Return 4.8 Reordering of Investigational Product Supply

5. Investigational Product Supply Order Forms

6. Investigational Product Receipt Records

7. Randomization/Treatment Assignment Records

8. Investigational Product Accountability Records

Investigational Product Accountability Log (EZN-2285)

Investigational Product Accountability Log (Oncaspar®) For Canadian Sites Only

Oncaspar® (pegaspargase) Lot Number Log (non-Canadian sites)

9. Investigational Product Return Records

DFCI Protocol 11-001 Pharmacy Manual Table of Contents CONFIDENTIAL


Clinical Drug Return Record Form

10. Temperature Monitoring Logs

11. EZN-2285 (calaspargase pegol) Stability Reports

12. Study Correspondence

DFCI Protocol 11-001 Pharmacy Manual Section 1 - Study Personnel Contact List CONFIDENTIAL



Pharmacy Manual Section 1 - Study Personnel Contact List

Name/Title Study Role Contact For: Contact Information Lewis Silverman, MD Principal Investigator

Principal Investigator

Clinical questions/SAEs/General study questions

Dana-Farber Cancer Institute 450 Brookline Ave, SW 320 Boston, MA 02215 Phone: 617-632-6191 Fax: 617-632-5710 Email: [email protected]

Sarah Hunt, MPH Clinical Research Manager

Oversight of the Protocol and FDA Submissions

General study questions

Dana-Farber Cancer Institute 450 Brookline Ave, Dana 135 Boston, MA 02215 Phone: 617-632-5904 Fax: 617-632-3977 Email: [email protected]

Shahzadi Baluch, MBA Clinical Research Specialist

Study Monitor

Study start up and regulatory questions from consortium sites


Cailin Toomey, BSN, RN, CPHON Clinical ResearchNurse

Clinical Research Nurse

Clinical questions/SAEs


Rachael Brem, MPH Clinical Research Coordinator

Clinical Research Coordinator

Primary contact for: General study questions/ DFCI enrolled patients






Name/Title Study Role Contact For: Contact Information Samia Ahmed Clinical Research Coordinator

Clinical Research Coordinator

Secondary contact for: General study questions/ DFCI enrolled patients


Irene Franklin, PharmD Director, Drug Safety Surveillance Sigma-Tau Pharmaceuticals

Safety Monitor Primary contact for: SAE Reporting

9841 Washingtonian Blvd. Suite 500 Gaithersburg, MD 20878 Ph: 301-670-2183

908-541-8740 Fax: 301--354-5346 e-mail: [email protected]

Vincent Elliott Sr. Clinical Affairs Specialist

Study Drug Distribution/Return

Primary contact for: Study drug shipment and return requests Secondary contact for:

9841 Washingtonian Blvd. Suite 500 Gaithersburg, MD 20878 Ph: 301-670-1525 Fax: 301--354-5358 e-mail: [email protected]

Scott Rodgers Sr. Clinical Research Manager


Primary contact for: Secondary contact for: Study drug shipment and return requests






Name/Title Study Role Contact For: Contact Information Thomas Genna Sr. Director Clinical Affairs


Back-up contact


DFCI Protocol 11-001 Pharmacy Manual Section 2 – Protocol and Amendments CONFIDENTIAL

Version: V02 February 11, 2013


Pharmacy Manual

Section 2 - Protocol and Amendments

DFCI Protocol 11-001 Pharmacy Manual Section 3 – Investigational Product CONFIDENTIAL



Pharmacy Manual

Section 3 - Investigational Product 3.1 Description 3.1.1 EZN-2285

EZN-2285 (SC-PEG E. coli L-asparaginase; calaspargase pegol) will be supplied by Sigma-Tau Pharmaceuticals, Inc (Sigma-Tau). EZN-2285 is a PEGylated conjugate of L-asparaginase and is similar to the currently approved Oncaspar® (SS-PEG E. coli L-asparaginase). The source of the Escherichia coli (E. coli) L-asparaginase is the same for both products, though EZN-2285 uses a shorter and more stable succinimidyl carbamate (SC) linker, to link the PEG to the L-asparaginase, instead of the succinimidyl succinate (SS) linker found in the currently approved Oncaspar®. EZN-2285 is an isotonic sterile solution in phosphate-buffered saline, pH 7.3, for injection only. The solution is clear, colorless, and contains no preservatives. EZN-2285 is supplied in 5 mL single-use vials. EZN-2285 activity is expressed in International Units (IU). One IU of L-asparaginase is defined as that amount of enzyme required to generate 1 mol of ammonia per minute at pH 7.3 and 37C. Each single-use vial contains 3,750 IU/5 mL (750 IU/mL). Each milliliter of EZN-2285 contains:

SC-PEG E. coli L-asparaginase-750 IU; Monobasic sodium phosphate, USP-1.29 mg; Dibasic sodium phosphate, USP-5.58 mg; Sodium chloride, USP-8.50 mg; and Water for injection, USP-qs to 1.0 mL

3.1.2 Oncaspar® (pegaspargase) Oncaspar® is L-asparaginase (L-asparagine amidohydrolase) that is covalently conjugated to monomethoxypolyethylene glycol (mPEG). L-asparaginase is a tetrameric enzyme that is produced endogenously by E.coli and consists of identical 34.5 kDa subunits. Approximately 69 to 82 molecules of mPEG are linked to L-asparaginase; the molecular weight of each mPEG molecule is about 5kDA. Oncaspar® activity is expressed in International Units. One International Unit of L-asparaginase is defined as the amount of enzyme required to generate 1 micromole of ammonia per minute at pH 7.3 and 37oC. Oncaspar® is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3. Each milliliter contains 750 ± 150 IU of pegaspargase, dibasic sodium phosphate, USP (5.58 mg), monobasic sodium phosphate, USP, (1.20 mg) and sodium chloride, USP (8.50 mg) in water for injection, USP.



3.2 Supply 3.2.1 EZN-2285 (calaspargase pegol)

Sigma-Tau will supply all approved study sites with EZN-2285 for use in this study.

3.2.2 Oncaspar®

For study centers in the United States and Puerto Rico, Oncaspar® will not be supplied by Sigma-Tau. Study sites in the United States and Puerto Rico will be responsible for obtaining Oncaspar® from usual commercial supply chains. As Oncaspar® is not commercially available in Canada, the drug will be supplied by Sigma Tau.

3.3 Packaging and Labeling 3.3.1 EZN-2285 (calaspargase pegol)

EZN-2285 will be packaged in boxes containing one single-use 5 mL vial. Each box and vial supplied will contain a single panel label similar to the sample shown below.

Under no circumstance will the study medication (EZN-2285) be administered to patients not enrolled in Protocol DFCI 11-001 or be used other than as directed by the protocol. The site pharmacy must apply a label to the final prepared infusion bag. The label text should minimally contain the protocol number, patient ID number and/or patient initials, drug name, dose, and lot number. It will also include the following required regulatory caution statement: “Caution: New Drug - Limited by Federal (or United States) Law to Investigational Use”.



3.3.2 Oncaspar® Oncaspar® is supplied as a sterile solution in Type I single-use vials containing 3,750 IU of L-asparaginase per 5 mL solution. For Oncaspar® supplied by Sigma Tau (Canadian sites) the box and vial will contain the commercial label along with an auxiliary label specifying the supply is for the DFCI study 11-001. A sample of the label can be seen below.

The site pharmacy must apply a label to the final prepared infusion bag. The label text should minimally contain the protocol number, patient ID number and/or patient initials, drug name, dose, and lot number. For Canadian sites, additional labeling text required by Health Canada will be added to the final label applied to the infusion bag. 3.4 Storage 3.4.1 EZN-2285

Store EZN-2285 refrigerated at +2°C to +8ºC (36°F to 46°F). Use only one dose per vial; do not re-enter the vial. Discard unused portions. Do not save unused drug for later administration. Do not use EZN-2285 if the drug has been frozen or if the vial has been stored at room temperature (+15°C to +25°C; 59°F to 77°F) for more than 48 hours. If, during refrigerated storage, the storage temperature deviates from +2°C to +8ºC (36°F to 46°F), the affected product should be immediately removed from inventory and placed into refrigerated quarantine. Sigma-Tau (personnel contact details are provided in Section 1 of this manual) should be contacted immediately and provided with the storage temperature records covering the entire period of time the storage temperature deviated outside the prescribed range. Upon review of the storage temperature records provided by the study site, a determination of EZN-2285 stability and disposition will be made. Quarantined EZN-2285 must not be administered to study patients until such time that Sigma-Tau provides written documentation that the product’s stability was not affected by the temperature deviation. If it is determined that the stability of the quarantined product was affected, arrangements must be made to replace the inventory at the site and for the return of the quarantined product for testing and/or destruction.



EZN-2285 diluted in 0.9% sodium chloride is stable for up to 48 hours at room temperature (+15°C to +25°C; 59°F to 77°F) and for up to 72 hours at 4oC (39F). EZN-2285 is a biologic product that does not contain preservatives. Do not use if EZN-2285 has been shaken or vigorously agitated or is cloudy or discolored, or precipitate is present. If local institutional guidelines for the compounding of sterile products were more stringent (i.e., shorter) with respect to the time between preparation and administration, the local guidelines will take precedence. 3.4.2 Oncaspar®

Store Oncaspar® under refrigerated conditions at 2oC to 8oC (36oF to 46oF). Do not shake or freeze product. Protect from light. Discard unused portions. Do not save unused drug for later administration. Do not use Oncaspar® after the expiration date on the vial. Do not administer Oncaspar® if drug has been:

Frozen Stored at room temperature 15o-25oC (59o-77oF) for more than 48 hours Shaken or vigorously agitated

Additionally, as with all parenteral drug products, they should be inspected visually for particulate matter, cloudiness, or discoloration prior to administration, whenever solution and container permit. If any of these are present, discard the vial. 3.5 Temperature Excursions 3.5.1 EZN-2285 Do not use EZN-2285 if the drug has been frozen or if the vial has been stored at room temperature (+15°C to +25°C; 59°F to 77°F) for more than 48 hours. If, during refrigerated storage, the storage temperature deviates from +2°C to +8ºC (36°F to 46°F), the affected product should be immediately removed from inventory and placed into refrigerated quarantine. Sigma-Tau (personnel contact details are provided in Section 1 of this manual) should be contacted immediately and provided with the storage temperature records covering the entire period of time the storage temperature deviated outside the prescribed range. Along with communicating the excursion, the site pharmacist should determine whether any patients received study drug between the time of the excursion and the time the excursion was identified/reported. Upon review of the storage temperature records provided by the study site, a determination of EZN-2285 stability and disposition will be made. Quarantined EZN 2285 must not be administered to study patients until such time that Sigma-Tau provides written documentation that the product’s stability was not affected by the temperature deviation.



If it is determined that the stability of the quarantined product was affected, arrangements must be made to replace the inventory at the site and for the return of the quarantined product for testing and/or destruction. 3.5.2 Oncaspar®

Do not use Oncaspar® if the drug has been frozen or if the vial has been stored at room temperature (+15°C to +25°C; 59°F to 77°F) for more than 48 hours. If, during refrigerated storage, the storage temperature deviates from +2°C to +8ºC (36°F to 46°F), the affected product should be immediately removed from inventory and placed into refrigerated quarantine.

If it is determined that the stability of the quarantined Oncaspar® was affected, the product should not be used and should be handled per the institution standard operating procedure for commercial drugs (for US and Puerto Rico Sites). For Canadian sites, Sigma- Tau (personnel contact details are provided in Section 1 of this Manual) should be contacted immediately and provided with the storage temperature records covering the entire period of time the storage temperature deviated outside the prescribed range. Along with communicating the excursion, the site pharmacist should determine whether any patients received study drug between the time of the excursion and the time the excursion was identified/reported. Upon review of the storage temperature records provided by the study site, a determination of Oncaspar® stability and disposition will be made. Quarantined Oncaspar® must not be administered to patients until such time that Sigma- Tau provides written documentation that the product’s stability was not affected by the temperature deviation. If it is determined that the stability of the quarantined product was affected, arrangements must be made to replace the inventory at the site and for the return of the quarantined product for testing and/or destruction.



3.6 Investigational Product Stability Reports Stability testing of the individual components of EZN-2285 is ongoing. As stability results are obtained, a Drug Product Stability Report will be provided for filing in this section.

For Oncaspar® the expiration date is contained on the product label. No stability reports will be provided.

DFCI Protocol 11-001 Pharmacy Manual Section 4 – Pharmacy Procedures CONFIDENTIAL



Pharmacy Manual

Section 4 - Pharmacy Procedures

4.1 Investigational Product Receipt Upon receipt of each shipment of EZN-2285 (and Oncaspar® in Canada), the responsible pharmacist or designee must verify that the shipment was received in good condition. If there is a discrepancy with the shipment (i.e. broken vials, incorrect quantity, etc.) please contact Sigma-Tau immediately (see Section 1 for contacts and contact information). After receipt immediately store the product, refrigerated at +2°C to +8ºC (36°F to 46°F), in a secure, limited access area. It is recommended that the site pharmacist place a sticker with the protocol number on the vial at the time the EZN-2285 (and Oncaspar® in Canada) is received. Once new EZN-2285 (and Oncaspar® in Canada)is received from Sigma-Tau, the site pharmacist should unpack the vials from the shipper and keep them in refrigerated quarantine until notified in writing by Sigma-Tau to remove the vials from quarantine and place them in their inventory for use. The temperature recorder included with any shipped EZN-2285 (and Oncaspar® in Canada) should be returned immediately to Sigma-Tau for analysis. Once received and analyzed, if the recorder shows temperature was maintained during transit, Sigma-Tau will issue a statement to the site to release the quarantined vials into their inventory for use. If the temperature recorder shows refrigerated shipping conditions were not maintained, Sigma-Tau will work with the site pharmacist to return the vials and have replacement vials of EZN-2285 (and Oncaspar® in Canada) shipped to the site. Each time EZN-2285 (and Oncaspar® in Canada) is received by the site, the vials should be placed into refrigerated quarantine until notified in writing by Sigma-Tau to move them into their inventory for use. ** Maintain the original Clinical Site Shipment Request Form, packaging slip and shipping slip in the pharmacy.

4.2 Investigational Product Accountability

Accountability

Inventory and accountability must be maintained on all EZN-2285 vials received, dispensed, returned and destroyed. See Section 8 for the EZN-2285 Accountability Log. A separate accountability log must be maintained for each individual lot number of EZN-2285. Sites may log drug accountability per their institutional policies or use the EZN-2285 Accountability Log provided in Section 8. The NCI Drug Accountability Log is



acceptable. If using an alternative Drug Accountability Log, all of the following information must be documented on the Accountability Log:

1. Study Number (noted at top of form)

2. Date drug was dispensed or received

3. Subject ID (no./initials)

4. Dose

5. Quantity Dispensed or Received

6. Lot Number (noted at top of form)

7. Total Vials in Inventory (for lot number noted above)

8. Received by/Dispensed by (initials/date)

For Canadian sites, accountability procedures for Oncaspar® should be the same as

what is described above for EZN- 2285.

The study Monitor will perform accountability and reconciliation and will initial and date each entry upon verification at the time of each monitoring visit. The site Pharmacist or designee will sign and date at the bottom upon completion of the form. The Monitor will also sign and date the bottom of the Accountability Log upon its completion.

4.3 Randomization and Assignment to Treatment Patients are to be randomized in accordance with Section 4 (Registration and Randomization Procedures) of the DFCI study protocol 11-001. 4.4 Investigational Product Dispensing

EZN-2285 (and Oncaspar® in Canada) is intended for use only for patients who are properly consented and enrolled into Protocol 11-001. Under no circumstance will the study medication (EZN-2285 and Oncaspar® in Canada)be administered to patients not enrolled in DCFI Protocol 11-001 or be used other than as directed by the protocol. The Investigator or designee will maintain accurate records of all clinical supplies that are received, dispensed and returned/destroyed. Upon completion of preparation of the infusion, used or partially used vials should be discarded per institutional standard operating procedures. Unused vials should be stored at +2°C to +8ºC (36°F to 46°F) in a secure, limited access area. If there are unused vials remaining, either expired or at the end of the study, Sigma-Tau project manager or designee will coordinate the return to Sigma-Tau for destruction of product. 4.5 Dose Preparation



4.5.1 EZN-2285

EZN-2285 is clear, colorless, and free of particulates. EZN-2285 is a biologic product that contains no antimicrobial preservative. As with all parenteral drug products, aseptic technique should be used during the preparation of EZN-2285. Prior to administration, dilute EZN-2285 by adding the dose to a 100mL bag of 0.9% Sodium Chloride Injection, USP (normal saline, NS). EZN-2285 should not be prepared in Dextrose 5% in Water (D5W). Avoid excessive agitation; do not shake. Before administration, the solution should be inspected visually for particulate matter, cloudiness, and discoloration. Do not use the reconstituted solution if discolored or cloudy, or if particulate matter or precipitate is present

EZN-2285 should not be administered if the drug has been frozen, shaken, or vigorously agitated. As with all parenteral drug products, aseptic technique should be used during the preparation and administration of EZN-2285.

4.5.2 Oncaspar® For intravenous administration, give over a period of 1 to 2 hours in 100 mL of sodium chloride or dextrose injection 5%, through an infusion that is already running. After the solution is diluted for intravenous use, the solution should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2oC to 8oC (36oF to 46oF). Storage after dilution should not exceed 48 hours from the time of preparation to completion of administration. Protect infusion bags from direct sunlight. Do not administer Oncaspar® if the drug has been frozen, stored at room temperature for more than 48 hours, shaken or vigorously agitated. 4.6 Dose Administration 4.6.1 EZN-2285

EZN-2285, diluted in a 100 mL 0.9% sodium chloride bag, should be given through a running infusion line over a period of 1 hour. Avoid excessive agitation. DO NOT SHAKE. Do not use if cloudy or if precipitate is present.

Although EZN-2285 should be prepared in an infusion bag containing normal saline, EZN-2285 may be administered through a main line running D5W or normal saline. While compatibility with a combination of normal saline and D5W has not been tested, the combination is expected to be acceptable as well. EZN-2285 is also compatible with lines containing sodium bicarbonate. No compatibility studies of EZN-2285 and total parenteral nutrition (TPN) or antibiotics have been conducted, and therefore EZN-2285 should not be mixed with TPN or antibiotics. Also, co-administration with allopurinol or



rasburicase should not occur as there has been no compatibility studies conducted with EZN-2285. No filter is required for EZN-2285 administration.

Serious allergic reactions can occur in patients receiving Oncaspar® and can presumably occur with EZN-2285. The risk of serious allergic reactions is higher in patients with known hypersensitivity to other forms of L-asparaginase. Have available during and after the infusion: antihistamine, epinephrine, oxygen, IV corticosteroids and IV fluids. Observe patient for ONE hour after administration for signs of Hypersensitivity Reactions.

4.6.2 Oncaspar®

Pegaspargase (Oncaspar®) is commercially available and is not provided for this study to sites in the United States and Puerto Rico by Sigma-Tau or its affiliates. However, Sigma-Tau will supply Oncaspar® to Canadian sites. Sites are required to maintain a record of the lot numbers of drug dispensed to study patients of all commercial and noncommercial supplies of Oncaspar®. Sites may log drug accountability per their institutional policies or use the Oncaspar® Lot Number Log provided in Section 8 of this manual for this purpose. The recommended dose of Oncaspar® is 2,500 International Units/m2 intramuscularly or intravenously. Oncaspar® should be administered no more frequently than every 14 days.

When administered intravenously, Oncaspar® should be given over a period of 1 to 2 hours in 100 mL of sodium chloride or dextrose injection 5%, through an infusion that is already running. After the solution is diluted for intravenous use, the solution should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2oC to 8oC (36oF to 46oF). Storage after dilution should not exceed 48 hours from the time of preparation to completion of administration. Protect infusion bags from direct sunlight.

Serious allergic reactions can occur in patients receiving Oncaspar®. The risk of serious allergic reactions is higher in patients with known hypersensitivity to other forms of L-asparaginase. Have the following available during and after the infusion: antihistamine, epinephrine, oxygen, IV corticosteroids and IV fluids.

Observe patient for ONE hour after administration for signs of Hypersensitivity Reactions.

4.7 Investigational Product Return

The Investigator or designee will maintain accurate records of all clinical supplies that are received, dispensed and returned/destroyed. Upon completion of preparation of the infusion, used or partially used vials should be discarded per institutional standard operating procedures. Unused vials should be stored at +2°C to +8ºC (36°F to 46°F) in a secure, limited access area. If there are unused vials remaining, either expired or at the end of the study,



Sigma-Tau project manager of designee will coordinate the return to Sigma-Tau or destruction of product at the site. Do not destroy any unused vials unless directed by Sigma-Tau.

Return of EZN-2285 and Oncaspar® to Sigma-Tau will be required under the following circumstances:

The current lot is set to expire The completion of the study/study drug dosing Temperature excursions that require exchange of product and possible retesting

Sigma-Tau will notify site personnel when the current lot of EZN-2285 is set to expire. Upon notification, sites will need to inventory all current supply on site and communicate the current inventory to Sigma-Tau to facilitate the exchange of the product. Returns for expiring drug and the completion of study/study drug dosing will be done under ambient conditions. In the event of a temperature excursion requiring exchange of the product and possible re-testing of drug, Sigma-tau will arrange for the shipment of a preconditioned shipping container and temperature monitor to the site for return of drug. For all returns:

Sigma-Tau will authorize the return. If necessary (for some temperature excursions), Sigma-Tau will provide a pre-

conditioned shipping container to the site for the return of drug The site pharmacist will receive the Clinical Drug Return Record form (Section 9). The site Pharmacist or designee completes and signs the form and makes a

copy to be retained for in the pharmacy site file. The original completed Clinical Drug Return Record form should be sent with the returned drug supplies.

4.8 Reordering of Investigational Product Supply Initial Order

Once DFCI and Sigma-Tau Pharmaceuticals, Inc. have received the regulatory documents from the site along with the completed Investigational Product Order Form (Section 5), Sigma-Tau will order the initial supply for the site with delivery as close to 48 hours as possible.

Resupply

The site personnel are responsible for maintaining the appropriate quantity of supply. The pharmacist is responsible for ordering the drug by using the Investigational Product Order Form.



Product is expected to arrive at the site within 14 business days from ordering. Shipments will be made on Monday through Thursday. Urgent shipments can and will be made to the clinical site when necessary. Fax completed order forms to Vincent Elliott at Sigma-Tau. The fax number is listed below and on the form:

Sigma-Tau – Vincent Elliott Fax Number – (301) 354-5358

[email protected]

DFCI Protocol 11-001 Pharmacy Manual Section 5 - Investigational Product Supply Order Forms CONFIDENTIAL



Pharmacy Manual

Section 5 - Investigational Product Supply Order Forms

DFCI Protocol 11-001 Investigational Product Order Form

Date of Request:

Site No.:

Site Name:

Requested By: Phone:

e-mail:

Shipping Address:

Investigational Product Requested

Quantity in Inventory

(vials)

Quantity Requested

(vials)

EZN-2285 (calaspargase pegol) - 5mL single-use vial containing 3,750 IU/5 mL (750 IU/mL)

For Canadian Sites Only: Oncaspar® (pegaspargase)- 5mL single- use vial containing 3,750 IU/5 mL (750 IU/mL)

_______________________________________ _________________ Signature of Authorized Site Personnel Date

FAX or e-mail signed, completed form to: Vincent Elliott

Senior Clinical Affairs Specialist Sigma-Tau Pharmaceuticals, Inc.

FAX: 301-354-5358

e-mail: [email protected] Note to Study Site: Please store the original and other associated shipment documentation in the pharmacy manual

DFCI Protocol 11-001 Pharmacy Manual Section 6 – Investigational Product Receipt Records CONFIDENTIAL



Pharmacy Manual

Section 6 - Investigational Product Receipt Records

DFCI Protocol 11-001 Pharmacy Manual Section 7 - Randomization/Treatment Assignment Records CONFIDENTIAL



Pharmacy Manual

Section 7 - Randomization/Treatment Assignment Records

DFCI Protocol 11-001 Pharmacy Manual Section 8 - Investigational Product Accountability Records CONFIDENTIAL



Pharmacy Manual

Section 8 - Investigational Product Accountability Records



EZN-2285 (calaspargase pegol)/ Oncaspar® (pegaspargase) Accountability Logs

Investigational Product Accountability Log

DFCI Protocol 11-001 Randomized Comparison of Intravenous Calaspargase Pegol (SC-PEG asparaginase) and Intravenous Oncaspar® in Children and Adolescents with Acute Lymphoblastic Leukemia or Lymphoblastic LymphomaInvestigational Product: EZN-2285 (calaspargase pegol)

Dosage Form and Strength: 750 IU/mL- 5mL single-use vial (3,750 IU/vial)

Lot No.

Investigator Name:

Site Name:

Site Number:

Investigational Product Receipt Investigational Product Dispensing

Monitor Verified

(initals/date)

Date Received

Quantity Received

Received by

(initals/date)

Subject ID

(no./initials)

Date Dispensed

Dose (IU)

No. Vials Dispensed

Dispensed by

(initals/date)

Total Vials in Inventory

Investigational Product Accountability Log (For Canadian Sites Only)

DFCI Protocol 11-001 Randomized Comparison of Intravenous Calaspargase Pegol (SC-PEG asparaginase) and Intravenous Oncaspar® in Children and Adolescents with Acute Lymphoblastic Leukemia or Lymphoblastic LymphomaInvestigational Product: Oncaspar® (pegaspargase)


Lot No.

Investigator Name:

Site Name:

Site Number:

Investigational Product Receipt Investigational Product Dispensing

Monitor Verified

(initals/date)

Date Received

Quantity Received

Received by

(initals/date)

Subject ID

(no./initials)

Date Dispensed

Dose (IU)

No. Vials Dispensed

Dispensed by

(initals/date)

Total Vials in Inventory



Oncaspar® (pegaspargase) Lot Number Log

Oncaspar® (pegaspargase) Lot Number Log (US and Puerto Rico Only) Protocol Number: DFCI Protocol 11-001

Protocol Title: Randomized Comparison of Intravenous Calaspargase Pegol (SC-PEG asparaginase) and Intravenous Oncaspar® in Children and Adolescents with Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Investigator Name:

Study Site Name:

Site Number:

Product: Oncaspar® (pegaspargase)


Patient Study Number:

Patient Initials:

Dose No. Date Dose

(Units) Number of

Vials Lot

Number Expiration

date Initials

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

DFCI Protocol 11-001 Pharmacy Manual Section 9 – Investigational Product Return Records CONFIDENTIAL



Pharmacy Manual

Section 9 - Investigational Product Return Records

Clinical Drug Return Record Protocol Number:

DFCI Protocol 11-001 Site No. :

Investigator Name:

Date of Return:

Clinical Drug Description (Drug, Dosage Form, Lot No):

Testing DestructionReason for Return: (Please note any tracking numbers for this return)

Dispensed Drug Return For [Vendor] Use(check to verify receipt of each

product/comments) Patient ID

(No./Initials) Description of Returned Supplies

(number of [packages] & [units] per [package])

Undispensed Drug Return For [Vendor] Use(check to verify receipt of each

product/comments)

Quantity Description

Authorized Site Personnel Monitor

Printed Name Printed Name

Signature/Date Signature/Date

For [Vendor] Use

Date Received: Shipment Tracking Number:

Checked by/Date:

Discrepancies/Comments:

Ship Returned Drug To: [Vendor Name] Attn: [vendor contact]

[vendor address] [phone no]

Place original form with shipment. Make copy for filing with site records.

Form STPCA3-002.2 Version 01, March 23, 2009

DFCI Protocol 11-001 Pharmacy Manual Section 10 – Temperature Monitoring Logs CONFIDENTIAL



Pharmacy Manual

Section 10 – Temperature Monitoring Logs

Please note: If a copy of Temperature Monitoring Logs will not be kept in Section 10 of the Pharmacy Manual, please include a Note to File, documenting where Temperature Monitoring Logs are kept for this study.

DFCI Protocol 11-001 Pharmacy Manual Section 11 – EZN-2285 (calaspargase pegol) Stability Reports CONFIDENTIAL



Pharmacy Manual

Section 11 – EZN-2285 (calaspargase pegol) Stability Reports

DFCI Protocol 11-001 Pharmacy Manual Section 12 – Study Correspondence CONFIDENTIAL



Pharmacy Manual

Section 12 – Study Correspondence

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