Aucatzyl Dosage

Preparing the Patient for AUCATZYL Infusion

Receipt and storage of AUCATZYL

• AUCATZYL is supplied directly to the cellular therapy laboratory associated with the infusion center in the vapor phase of a liquid nitrogen shipper.
  Confirm the patient's identity on the infusion bags with the patient identifiers on the shipper, see Figure 2.

Figure 2: Patient Specific Identifiers

• Keep the infusion bag(s) in the metal cassette(s) and transfer AUCATZYL to the onsite controlled-access vapor phase of liquid nitrogen for storage below minus 150°C until ready for thaw and administration.
  • Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds).

Planning prior to AUCATZYL preparation

• The patient batch specific Release for Infusion certificate and Dose Schedule Planner will be provided in the shipper and via Autolus's Scheduling Portal.
• Confirm the patient identifiers on the Release for Infusion certificate and infusion bags match, see Figure 2.

1. Ensure the patient's bone marrow assessment results are available.
   NOTE: The patient's bone marrow assessment results will be used to select the appropriate dosing regimen based on a Bone Marrow Blast of > 20% or ≤ 20%, see Figure 3.
2. The AUCATZYL Dose Schedule Planner is provided with the Release for Infusion certificate and assists the determination of the appropriate dose regimen to be administered on Day 1 (3 days (± 1 day) after the completion of lymphodepleting chemotherapy) and Day 10 (± 2 days). Record the following information on the Dose Schedule Planner:
   1. The blast percentage from the patient's bone marrow assessment.
   2. The AUCATZYL bag serial number(s); number of bag type required for each dose; and the specified volume to administer via syringe (for the 10 × 106 dose, Blue Bag) transcribed from the Release for Infusion certificate.
3. The completion of the AUCATZYL Dose Schedule Planner will guide the treating physician on the number of bags required and preparation of AUCATZYL for the Day 1 and Day 10 (± 2 days) dose, see Figure 3.

Transfer and Thawing

• Using the completed Dose Schedule Planner for guidance, transfer ONLY the cassette(s)/ infusion bag(s) required for the given dosing day from the onsite vapor phase liquid nitrogen storage to an appropriate transfer vessel (i.e., a vapor phase liquid nitrogen shipper, maintaining a temperature below minus 150°C) for transport to the bag thaw location.
• Transfer the required cassette(s) one by one, confirming the AUCATZYL bag serial numbers and patient identifiers on each infusion bag label, see Figure 2.
• Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds).
• If more than one infusion bag is required on a given dosing day, thaw each infusion bag one at a time; Do NOT remove subsequent bags from the vapor phase liquid nitrogen storage (below minus 150°C) until the infusion of the previous bag is complete.
• AUCATZYL must be continuously monitored during thawing process.
• Leave the AUCATZYL infusion bag in its overwrap, thaw at 37°C using a water bath or dry thaw method until there are no visible frozen clumps left in the infusion bag. Each bag should be gently massaged until the cells have just thawed. Thawing of each infusion bag takes between 2 and 8 minutes. Remove from water bath or thaw device immediately after thawing is complete. Carefully remove the infusion bag from the overwrap taking care to avoid damage to the bag and ports.
• Gently mix the contents of the bag to disperse clumps of cellular material and administer immediately to the patient.
• Do not re-freeze or refrigerate thawed product.

Figure 3: AUCATZYL Dosage and Schedule

* Refer to Release for Infusion Certificate for the exact volume to be administered via syringe. Withdraw ONLY the volume. † The 100 × 106 (Orange Bag) and 300 × 106 (Red Bag) doses will be suspended in one or more infusion bags.
Bone Marrow Blast > 20%
Day 1		Day 10 (± 2 days)
10 × 106 Dose administered via syringe*		100 × 106 Dose administered via bag infusion† and 300 × 106 Dose administered via bag infusion†
Bone Marrow Blast ≤ 20%
Day 1		Day 10 (± 2 days)
100 × 106 Dose administered via bag infusion†		10 × 106 Dose administered via syringe* and 300 × 106 Dose administered via bag infusion†

Dose administration for 10 × 106 CD19 CAR-positive viable T cell Dose (Blue Bag)

Withdrawal of the 10 × 106 dose into the syringe should be carried as follows:

• Prepare and administer AUCATZYL using aseptic technique.
• Gently mix the contents of the bag to disperse clumps of cellular material.
• The volume to be administered for the 10 × 106 dose (Blue Bag) is specified on the Release for Infusion certificate.
• Use the smallest Luer-lock tip syringe necessary (1, 3, 5, or 10 mL) with a Luer-lock bag spike to draw up the volume as specified on the Release for Infusion certificate.
  • Do NOT use a leukodepleting filter.
  • Do NOT use the syringe to mix the cells, see Figure 4.

Figure 4: Syringe Infusion Guidance for the 10 × 106 Dose (Blue Bag)

Withdraw the volume from the 10 × 106 Dose (Blue Bag) specified on the Release for Infusion certificate using a syringe fitted with a bag spike.		Do not use the syringe to mix the cells		Confirm withdrawal of the exact volume specified on the Release for Infusion certificate for the 10 × 106 Dose (Blue Bag).

• Prime the tubing with normal saline prior to infusion.
• Once AUCATZYL has been drawn into the syringe, verify the volume and administer as an intravenous infusion as soon as possible as a slow push (approximately 0.5 mL/minute) through a central venous line (or large peripheral venous access line appropriate for blood products).
• Complete infusion at room temperature within 60 minutes post thaw and flush the tubing line with 60 mL of normal saline.
• Dispose of any unused portion of AUCATZYL (according to local biosafety guidelines).

Dose administration for 100 × 106 (Orange Bag) and/or 300 × 106 (Red Bag) CD19 CAR-positive viable T cells

Refer to the Release for Infusion certificate and Dose Schedule Planner for the following details:

• The volume and total CD19 CAR-positive viable T cell number contained in each infusion bag.
• The dose to be administered on the given dosing day and the number of bags required to deliver the specified CD19 CAR-positive viable T cell dose.
• If more than one bag is needed, thaw subsequent bags after the previous bag is fully administered.

1. Prime the tubing with normal saline prior to infusion.
2. Administer AUCATZYL via a gravity or peristaltic pump assisted IV infusion through a central venous line (or large peripheral venous access line appropriate for blood products).
   • Do NOT use a leukodepleting filter.
   • Aseptic techniques must be applied when performing a venepuncture, spiking the ports, and through the cell administration process.
   • Gently mix the contents of the bag during AUCATZYL infusion to disperse cell clumps.
3. Infuse the entire content of the AUCATZYL infusion bag at room temperature within 60 minutes post thaw (infusion rate within 0.1 to 27 mL/minute).
   • After the entire content of the infusion bag is infused, rinse the bag with 30 mL of normal saline, then flush the tubing line with 60 mL of normal saline.
   • Repeat steps 1 - 3 for any additional infusion bags required on the given dosing day. Do NOT initiate thaw of the next bag until infusion of the previous bag is complete.

AUCATZYL contains human blood cells that are genetically modified with replication -incompetent lentiviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal of AUCATZYL to avoid potential transmission of infectious diseases.