Usual Adult Dose for Thalassemia

Minimum recommended dose:
Intravenous infusion of 5.0 × 10(6) CD34+ cells/kg

Maximum dose:
Intravenous infusion of 42.1 × 10(6) CD34+ cells/kg

Comments:

• Prior to initiating mobilization, apheresis, and myeloablative conditioning, ensure that hematopoietic stem cell (HSC) transplantation is appropriate for the patient.
• Do not initiate myeloablative conditioning until the complete dose is received and stored at the treatment center and the availability of the backup collection is confirmed.
• Stop iron chelation at least 7 days before administering myeloablative conditioning; full myeloablative conditioning is required followed by a minimum of 48 hours of washout before infusion of this product.
• It is advised to maintain the hemoglobin (Hb) level at 11 g/dL or higher for at least 30 days before mobilization and myeloablative conditioning.
• In clinical studies, granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization, and busulfan was used for myeloablative conditioning prior to treatment.
• Using the lot information sheet, confirm the total number of infusion bags that need to be administered.
• Infuse each bag over less than 30 minutes.
• If the minimum dose of 5.0 × 10(6) CD34+ cells/kg is not met, then additional cycles of mobilization and apheresis may be required, separated by at least 14 days, to obtain more cells for additional manufacturing.

Usual Pediatric Dose for Thalassemia

Minimum recommended dose:
Intravenous infusion of 5.0 × 10(6) CD34+ cells/kg

Maximum dose:
Intravenous infusion of 42.1 × 10(6) CD34+ cells/kg

Comments:

• Prior to initiating mobilization, apheresis, and myeloablative conditioning, ensure that hematopoietic stem cell (HSC) transplantation is appropriate for the patient.
• Do not initiate myeloablative conditioning until the complete dose is received and stored at the treatment center and the availability of the backup collection is confirmed.
• Stop iron chelation at least 7 days before administering myeloablative conditioning; full myeloablative conditioning is required followed by a minimum of 48 hours of washout before infusion of this product.
• It is advised to maintain the hemoglobin (Hb) level at 11 g/dL or higher for at least 30 days before mobilization and myeloablative conditioning.
• In clinical studies, granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization, and busulfan was used for myeloablative conditioning prior to treatment.
• Using the lot information sheet, confirm the total number of infusion bags that need to be administered.
• Infuse each bag over less than 30 minutes.
• If the minimum dose of 5.0 × 10(6) CD34+ cells/kg is not met, then additional cycles of mobilization and apheresis may be required, separated by at least 14 days, to obtain more cells for additional manufacturing.
• Pediatric patients as compared to adults took longer Engraftment time.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 4 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This product is for autologous and one-time single-dose intravenous use only.
• Prior to administration, confirm that the patient(s) identity matches the unique patient identifiers located on this product(s) metal cassette(s), infusion bag(s), and lot information sheet upon receipt.
• Do not infuse this product if the information on the patient-specific label does not match the intended patient.
• Thaw this product prior to infusion; do not use an in-line blood filter or an infusion pump.
• If more than one infusion bag is provided, administer each infusion bag completely prior to proceeding to thaw and infuse the next infusion bag.
• Administer the product completely within 4 hours after thawing.
• Up to two drug product lots can be administered to meet the target dose.
• Follow standard procedures for patient management after HSC transplantation after this product infusion.
• Any blood products required within the first 3 months after infusion of this product should be irradiated.
• G-CSF use is not recommended for 21 days after infusion of this product.
• Resume iron chelation or phlebotomy after infusion of this product, if required.
• Evaluate for renal and hepatic impairment to ensure an appropriate HCC transplant.
• A negative HIV test is necessary to ensure acceptance of apheresis material for the manufacturing of this product.

• Store at less than or equal to -140C (less than or equal to -220F) in the vapor phase of liquid nitrogen until ready for thaw and administration.
• Do not re-freeze after thawing.
• Do not irradiate this product, as this could lead to inactivation.
• If there are any concerns about the product or packaging upon receipt, contact Bluebird Bio at 1-833-999-6378.

• Remove infusion bags from the metal cassettes, which are stored in liquid nitrogen storage.
• Confirm the product name printed on the infusion bag(s).
• Confirm that the patient identity matches the unique patient identifiers located on the product infusion bag(s).
• Verify the number of infusion bags present is correct and ensure that the infusion bag(s) are within the expiration date, using the lot information sheet.
• Examine infusion bag(s) for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow local guidelines, and contact Bluebird Bio immediately at 1-833-999-6378.
• Thaw each infusion bag of this product at 37C (98.6F) in a water bath or dry bath.
• Thawing takes approximately 2 to 4 minutes; do not leave the infusion bags unattended or submerge the infusion ports in a water bath.
• After thawing, gently mix the contents by massaging the infusion bag and dispersing clumps of cellular material until the contents are uniform.
• If visible cell clumps remain, continue to gently mix the contents of the bag.
• Most small lumps of cellular material should disperse with gentle manual mixing.
• Do not filter, wash, spin down, and/or resuspend this product in new media prior to infusion.
• Do not sample, alter, irradiate, or refreeze this product.

• Institute appropriate therapy for the prophylaxis of hepatic veno-occlusive disease (VOD) and seizures.
• Test for the presence of hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotrophic virus 1 and 2 (HTLV-1/HTLV-2), and human immunodeficiency virus 1 and 2 (HIV-1/HIV-2) in accordance with clinical guidelines prior to collecting cells for manufacturing.
• HSC mobilization followed by apheresis is required to obtain the target number of CD34+ cells (more than or equal to 12 × 10(6) CD34+ cells/kg) from patients for the manufacturing of this product.
• Collect 1.5 × 10(6) CD34+ cells/kg or more (via apheresis); or more than 1.0 × 10(8) total nucleated cells/kg (via bone marrow harvest) from the patient and cryopreserve them as a backup before myeloablative conditioning. These may be needed in rescue treatment if hematopoietic stem cells or this product are compromised prior to infusion, primary engraftment fails, or loss of engraftment occurs after infusion of this product.
• Confirm the infusion time in advance to coordinate the timing of thawing and infusion in such a way that it will be available for infusion when the patient and healthcare providers are ready.
• Follow universal precautions and biosafety guidelines (Biosafety Level 2) for the handling and disposal of this product to avoid the potential transmission of infectious diseases.

• Hematologic: Platelet counts, absolute neutrophil counts, thrombocytopenia, and bleeding (periodically during and after therapy).
• Oncologic: Hematologic malignancies with a complete blood count.
• Hypersensitivity: Hypersensitivity reactions during therapy.

• Read the US FDA-approved patient labeling (Patient Information).
• There is a risk of manufacturing failure associated with this product, which may require additional cell collection and manufacturing of this product.
• Seek immediate medical attention if new or worsening bleeding or bruising occurs after infusion of this product.
• Platelet recovery following infusion of this product could be delayed, resulting in an increased risk of bruising or bleeding.
• Watch for signs and symptoms of bleeding and have frequent blood draws for platelet counts until platelet recovery has been achieved.
• Have the treating physician contact Bluebird Bio at 1-833-999-6378 if malignancy is diagnosed, due to the potential risk of blood cancer associated with this treatment.
• Do not donate blood, organs, tissues, or cells in the future after receiving this drug.
• After treatment with this product, some commercial tests may give a false-positive human immunodeficiency virus (HIV) test result.
• Contact your healthcare provider immediately if new or unusual bleeding is observed, including any signs or symptoms suggestive of a severe headache, abnormal bruising, unusual stomach or back pain, nose bleeding, coughing up blood, or blood in urine, stool, or vomit.
• Test for any changes in blood at least yearly for at least 15 years.