omidubicel (Rx)

>10%

Magnesium decreased, Grade 1-4 (94%)

Viral infections, Grade 1-3 (75%)

Bacterial infections, Grade 1-3 (65%)

Acute GVHD, Grade 2-4 (62%)

AST increased, Grade 1-4 (56%)

ALT increased, Grade 1-4 (56%)

Creatinine increased, Grade 1-4 (50%)

Bilirubin increased, Grade 1-4 (42%)

Alkaline phosphatase increased, Grade 1-4 (42%)

Chronic GVHD (35%)

Pain (33%)

Mucosal inflammation (31%)

Hypertension (25%)

Fungal infections, Grade 1-3 (21%)

Disease relapse (21%)

Gastrointestinal toxicity (19%)

Magnesium increased, Grade 1-4 (15%)

Hemorrhage (12%)

Dysphagia (12%)

Renal impairment (12%)

Respiratory failure (12%)

1-10%

Dyspnea (8%)

Fatigue (4%)

Graft failure (2%)

Fever (2%)

Contraindications

Known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin or bovine material

Cautions

Infusion reactions occurred following infusion, including hypertension, mucosal inflammation, dysphagia, dyspnea, vomiting and gastrointestinal toxicity; monitor for signs and symptoms of infusion reactions during and after administration

Acute and chronic GVHD, including life-threatening and fatal cases, occurred following treatment; acute GVHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin level

Primary graft failure occurred; immunologic rejection is primary cause of graft failure

Engraftment syndrome may occur; monitor for unexplained fever, rash, hypoxemia, weight gain, and pulmonary infiltrates in the periengraftment period; treat with corticosteroids as soon as engraftment syndrome is recognized, to ameliorate symptoms; if untreated, engraftment syndrome may progress to multiorgan failure and death

Transmission of serious infections

• Transmission of infectious disease may occur
• Disease may be caused by known or unknown infectious agents
• Screen donors for increased risk of infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, West Nile Virus (WNV), transmissible spongiform encephalopathy (TSE) agents, vaccinia, and Zika virus (for umbilical cord blood collected since March 2016)
• Also screen donors for clinical evidence of sepsis and communicable disease risks associated with xenotransplantation
• Test maternal blood samples for HIV types 1 and 2, HTLV types I and II, HBV, HCV, T pallidum, and WNV
• Testing of maternal and infant donor blood is also performed for evidence of donor infection due to cytomegalovirus
• Test results may be found on container label and/or in accompanying records
• Report occurrence of transmitted infection to Gamida Cell at (844) 477-7478
• These measures do not totally eliminate risk of transmitting infectious diseases and disease agents

Transmission of rare genetic diseases

• May transmit rare genetic diseases involving the hematopoietic system
• Screen cord blood donors to exclude donors with sickle cell disease, and anemias due to abnormalities in hemoglobins C, D, and E
• Because of the age of donor at time cord blood collection takes place, the ability to exclude rare genetic diseases is severely limited

Allergic reactions

• Allergic reactions may occur
• Reactions include bronchospasm, wheezing, angioedema, pruritus, and hives
• Serious hypersensitivity reactions, including anaphylaxis, may be due to DMSO, residual gentamicin, Dextran 40, human serum albumin (HSA), and bovine material in omidubicel
• May also contain residual antibiotics if cord blood donor was exposed to antibiotics in utero
• Monitor patients with a history of allergic reactions to antibiotics for allergic reactions after administering

Malignancies of donor origin

• Two treated patients developed post-transplant lymphoproliferative disorder (PTLD) in the second year post-transplant
• PTLD manifests as a lymphoma-like disease favoring non-nodal sites
• PTLD is usually fatal if not treated
• Etiology is thought to be donor lymphoid cells transformed by Epstein-Barr virus (EBV)
• Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias
• One treated patient developed a donor-cell derived myelodysplastic syndrome (MDS) during the fourth year posttransplant
• Natural history is presumed to be the same as that for de novo MDS
• Monitor life-long for secondary malignancies
• In event that a secondary malignancy occurs after treatment, contact Gamida Cell at (844) 477-7478

Pregnancy

No data are available on use in pregnant females

No animal reproductive and developmental toxicity studies have been conducted to assess whether it can cause fetal harm when administered to pregnant females

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus

Verify pregnancy status of females with reproductive potential

Contraception

• See the prescribing information for medications used for conditioning for information on need for effective contraception in patients who receive a conditioning regimen
• There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment

Lactation

There is no information regarding presence of omidubicel in human milk, effect on breastfed infants, and effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Nicotinamide (NAM)-modified allogeneic hematopoietic progenitor cell (HPC) therapy derived from cord blood used as an allogeneic stem cell donor source

Manufactured utilizing a proprietary NAM-based technology producing enriched HPCs

NAM technology overcomes the induction of accelerated proliferation, differentiation, cellular stress, and signaling pathways that are typically activated when HPCs are removed from their natural environment

Ex-vivo culturing of cord blood–derived HPCs in the presence of NAM leads to preservation of their stemness, homing to the bone marrow (BM) and retained engraftment capacity, as demonstrated by rapid neutrophil engraftment and multilineage immune reconstitution as observed in the clinical trials

General Considerations Before Preparation

Match patient’s identity with patient-specific identifiers on CF and NF metal cassettes, CF and NF bags, and infusion solutions for CF and NF bags

Do NOT infuse if patient-specific labels do not match intended patient

Confirm Released for Infusion Certificate (RFI Certificate) is available before starting conditioning regimen

Administer appropriate conditioning regimen before infusion, according to institutional guidelines

Administer prophylactic and supportive therapies for prevention or treatment of transplant complications (GVHD, infections) according to institutional guidelines

Confirm emergency medications are available before infusing and during recovery period as per institutional guidelines

Refer to prescribing information in regard to receiving drug shipment

Planning before preparation

• Do NOT prepare until after receipt of RFI Certificate for this patient-specific batch
• RFI certificate will be issued via Gamida Cell Assist Hospital Portal up to 72 hr after completion of manufacturing
• Confirm receipt of RFI Certificate
• Confirm patient-specific identifiers on RFI Certificate and CoAs match patient’s identity

IV Preparation

Follow universal precautions and guidelines for handling and disposal of human cells to avoid potential transmission of infectious disease

Use aseptic technique for all processing steps; do NOT draw samples from infusion bags

CF bag

• Preparing infusion bag

  • Remove only IS for CF bag from the 2-8ºC storage location
  • Confirm patient-specific identifiers on label of IS for CF match intended patient
  • Wipe IS for CF sterile bag with 70% alcohol; place in biological safety cabinet (BSC) (if available), for at least 20 min and not to exceed 24 hr, at room temperature
  • Before dilution, remove IS for CF bag from its sterile bag; ensure pinch clamp is closed

• Thawing CF

  • Remove CF metal cassette from the liquid nitrogen storage
  • Before opening CF metal cassette, verify patient-specific identifiers on cassette and on CF cryopreserved bag match intended patient
  • Once verified, open CF metal cassette to remove CF cryopreserved bag from cassette
  • Leave CF cryopreserved bag in overwrap bag during thawing and dilution
  • Visually inspect the CF cryopreserved bag for damage; if damaged, contact Gamida Cell at (844) 477-7478; cryopreserved CF should be white in color
  • Once CF cryopreserved bag is removed from cassette, thaw and dilution must be carried to completion and cells administered within 2 hr post-dilution
  • Incubate CF cryopreserved bag for 5 minutes at room temperature
  • Place cryopreserved bag in an ~37ºC water bath until product reaches a liquid consistency; generally, takes about 3-8 minutes; do not massage, knead or apply pressure on the product bag
  • Keep bag fully submerged until thawed – do not remove before thawing completion
  • Remove bag from water bath once completely thawed; do not remove overwrap bag
  • Wipe overwrap with 70% alcohol; put bag into the BSC (if available)
  • Wipe a pair of clean scissors with 70% alcohol; cut sealed area at top of overwrap; be careful not to damage CF bag or CF bag’s ports/tubing
  • Insert spike adapter attached to IS for CF bag into one of CF bag ports, while it remains in overwrap bag

• Dilution of CF bag

  • Open pinch clamp on the IS tubing and double volume of CF by adding IS for CF (~20 mL) to CF bag; gently swirl the bag until mixed well
  • Add remaining IS for CF (approximately 60 mL) to the CF bag; close valve and swirl gently
  • Remove overwrap of CF bag and check the integrity of CF bag
  • Check appearance of the contents of the CF bag; diluted CF should appear as a yellowish suspension, essentially free of visible white clumps and foreign particulates
  • Inspect the contents of the thawed and diluted CF bag for any visible cell clumps; if visible cell clumps remain, gently invert the bag and/or massage it with fingertips; disperse small clumps of cellular material with gentle manual mixing
  • Do not infuse CF if clumps are not dispersed, the bag is damaged or leaking, or otherwise appears to be compromised; if this occurs, call Gamida Cell at (844) 477-7478
  • Heat seal and detach emptied IS for CF bag
  • Connect transfusion infusion set to the free port on the CF bag
  • Place CF bag containing the thawed and diluted CF in a new sterile bag; do not wash, spin down, and/or resuspend CF in new media before infusing
  • Transport product to patient at room temperature; transport to patient’s bedside in a closed box/bag to protect product; completely infuse CF bag within 2 hr post-dilution

NF bag

• Preparing and thawing infusion bag

  • Repeat the same steps used for CF bag
  • Note: Once NF cryopreserved bag is removed from cassette, thaw and dilution must be carried to completion and cells administered within 1 hr post-dilution

• Diluting bag

  • Insert the spike adapter attached to the IS for NF bag into one of the ports of the NF bag, while it remains in the overwrap bag
  • Open pinch clamp on the IS tubing and double the volume of the NF by adding IS for NF (~10 mL) to the NF bag; gently swirl the bag until mixed well
  • Add remaining IS for NF (~30 mL) to the NF bag; close the valve and swirl gently
  • Remove overwrap of CF bag and check the integrity of CF bag
  • Thawed and diluted NF should appear as a reddish suspension free of visible clumps and foreign particulates
  • Inspect the contents of thawed and diluted NF bag for any visible cell clumps; if visible cell clumps remain, gently invert the bag and/or massage it with fingertips; disperse small clumps of cellular material with gentle manual mixing
  • Do not infuse NF if clumps are not dispersed, the bag is damaged or leaking, or otherwise appears to be compromised; if this occurs, call Gamida Cell at (844) 477-7478
  • Heat seal and detach emptied IS for NF bag
  • Connect transfusion infusion set to free port on the NF bag
  • Place CF bag containing the thawed and diluted CF in a new sterile bag; do not wash, spin down, and/or resuspend CF in new media before infusing
  • Transport product to patient at room temperature; transport to patient in a closed box/bag; completely infuse NF bag within 1 hr post-dilution

Premedication

Premedicate 30-60 minutes before infusing

Premedicate with

• Diphenhydramine 50 mg IV (or 0.5 mg/kg [do not exceed 50 mg/dose]) or dexchlorpheniramine 10 mg IV AND
• Hydrocortisone 50 mg IV (or 0.5 mg/kg [do not exceed 50 mg/dose]) AND
• Acetaminophen 650 mg PO (or 10 mg/kg [do not exceed 650 mg])
• Avoid prophylactic use of methylprednisolone in conjunction with omidubicel
• Ensure patient is adequately hydrated

IV Administration

For IV use only; central venous access is recommended

Do not irradiate

Do NOT use a leukodepleting filter

Confirm patient’s identity matches the patient-specific identifiers on the CF and NF bags

Administration should be under supervision of healthcare provider experienced in hematopoietic stem cell transplantation (HSCT)

Administer by gravity infusion

Prior to spiking both CF and NF bags, prime infusion set tubing with 0.9% NaCl

Infuse entire contents of CF and NF bags

Infusion rate should not exceed 10 mL/kg/hr

Thawed and diluted CF bag must be infused FIRST

Infusion time should not exceed 2 hr from end of dilution to end of CF infusion

If an infusion reaction occurs, appropriately manage reaction before thawing NF bag

Thawed and diluted NF is infused within 1 hr of safely administering CF infusion

Infusion time should not exceed 1 hr from end of dilution to end of infusion

In event of any deviation from dosing schedule, contact Gamida Cell at (844) 477-7478

After entire contents of the CF and NF bags are each infused, flush tubing with 0.9% NaCl at same infusion rate to ensure as many cells as possible are delivered to patient

Follow universal precautions and local biosafety guidelines for handling and disposal of human cells to avoid potential transmission of infectious diseases

Storage

CF and NF metal cassettes

• Store frozen in vapor phase of liquid nitrogen (≤-150ºC) in a temperature-controlled system

IS bags

• Refrigerate at 2-8ºC until time of thaw of CF and NF

Cryopreserved bag removed from cassette

• CF: Thaw and dilution must be completed and cells administered within 2 hr post-dilution
• NF: Thaw and dilution must be completed and cells administered within 1 hr post-dilution