Usual Pediatric Dose for Cerebral Adrenoleukodystrophy

Minimum recommended dose: 5.0*10(6) CD34+ cells/kg as a single dose for intravenous infusion

Comments:

• This indication is approved under accelerated approval based on 24-month major functional disability (MFD)-free survival.
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
• The eligibility for early, active cerebral adrenoleukodystrophy (CALD) is defined as asymptomatic or mildly symptomatic (neurologic function score, NFS 1 or less) patients who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9.
• Dose calculation is based on individual body weight prior to first apheresis. Refer to manufacturer product information for detailed calculation.
• This drug product is not indicated for prevention of development or treatment of adrenal insufficiency due to adrenoleukodystrophy.
• This drug product has not been studied in patients with cerebral adrenoleukodystrophy (CALD) secondary to head trauma.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Data not available

Precautions

US BOXED WARNING: Hematologic malignancy

• This drug product may cause life-threatening cases of myelodysplastic syndrome. In patients treated with this drug product, malignancy was diagnosed between 14 months to 7.5 years post administration and appeared to be a result of lentiviral vector, Lenti-D, integration in proto-oncogenes.
• Patients should be monitored closely for any malignancy through complete blood counts every 6 months and through assessments for evidence for clonal expansion or predominance at least twice in the first year and annually thereafter. Bone marrow should also be evaluated as per clinical need.

Dialysis

Data not available

Other Comments

Administration advice:

• This preparation is for autologous use only.
• The patient's identity must match the unique patient identifiers on the infusion bag.
• The number of infusion bags to be administered should be confirmed from lot information sheet.
• Refer to manufacturer product information for detailed instructions.

• This drug product is stored in the vapor phase of liquid nitrogen at less than or equal to minus 140C (minus 220F) until ready for thaw and administration.
• Thawing should be done before administration.
• Do not re-freeze after thawing.
• This drug product should not be irradiated as it may cause inactivation.

• Refer to manufacturer product information for detailed instructions.

• Patient should be advised to read the FDA-approved patient labeling.
• Patients should be informed about the risk of manufacturing failure. In case of any failure in the manufacturing process, additional cell collection may be required.
• Patients should be informed about unexplained efficacy failure that has occurred with this treatment.
• Patients should be informed about the potential of this treatment to cause hematologic malignancy that can be life-threatening.
• Many patients have been diagnosed with myelodysplastic syndrome (MDS) after the treatment and the only cure for this condition is another bone marrow transplant, with or without the addition of chemotherapy and total body irradiation.
• Patients should be informed about periodic monitoring for hematological malignancy by blood tests at least every 6 months, for a minimum of 15 years.
• Patients should be advised about the need for frequent blood tests and invasive bone marrow biopsies if there is any concern of malignancy.
• Patients should be careful about development of any signs or symptoms of malignancy including fatigue or easy bleeding or bruising, and contact bluebird bio at 1-833-999-6378, if they are diagnosed with a hematologic malignancy.
• Inform patients about the possible need for an allogeneic hematopoietic stem cell transplant in the event of efficacy failure or hematologic malignancy with this treatment. Continuous monitoring for these complications is required.
• Patients may develop severe infections, including life-threatening infections for which prolonged hospitalization may be required.
• Inform patients about the occurrence of prolonged cytopenias during treatment and that frequent blood tests may be needed until blood counts return to normal.
• Patients should immediately reach out to their health care provider in case of any signs and symptoms of thrombocytopenia, neutropenia, or anemia, such as easy bleeding, serious infections, or fatigue.
• Patients should be informed about the risk of bleeding and that the need for platelet transfusion is likely after myeloablative conditioning.
• Inform patients about the risk of neutrophil engraftment failure with this treatment and in such events, a rescue treatment is required with their back-up collection of CD34+ cells.
• Inform patients about HBV, HCV, HIV, and HTLV screening before initiation of this treatment.
• Patients may falsely test positive for HIV after this treatment if using a PCR test. Patients are advised to inform any healthcare providers about this possibility before being tested for HIV.
• Patients treated with this drug product should not donate blood, organs, tissues, or cells anytime in the future.