Omidubicel is a nicotinamide-modified allogeneic hematopoietic progenitor cell therapy derived from cord blood indicated for use in adults and pediatric patients 12 years and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. Omidubicel has a black box warning for infusion reactions, graft-vs-host disease, engraftment syndrome, and graft failure.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect the thawed and diluted Cultured Fraction (CF) and Noncultured Fraction (NF) bags for any visible cell clumps. Gently invert and/or massage the bag with fingertips to disperse visible cell clumps. Do not administer if clumps do not disperse or the bag is damaged or leaking and call Gamida Cell at 1-844-477-7478.
The thawed and diluted CF should appear as a yellowish suspension; the thawed and diluted NF should appear as a reddish suspension.
Follow universal precautions and local biosafety guidelines for handling and disposal of human cells to avoid potential transmission of infectious diseases.
Intravenous Administration
-For comprehensive preparation, storage, and administration information, refer to the Administration section of the Full Prescribing Information for omidubicel.
-A single dose of omidubicel consists of 2 fractions: a cultured fraction (CF) and a noncultured fraction (NF).
-Do not open the metal cassettes containing the CF and NF cryopreserved bags until the time of thaw; thaw immediately prior to use.
-Dilution of each cryopreserved bag is required prior to infusion; use the provided infusion solution that is specific to each fraction.
-Do not wash, spin down, and/or resuspend CF or NF in new media prior to infusion; additionally, do not irradiate.
-Verify the patient's identity upon receipt of omidubicel, prior to thaw, and prior to the infusion.
-Confirm emergency medications are available prior to infusion and during the recovery period.
-Premedicate patients with acetaminophen, an antihistamine, and hydrocortisone approximately 30 to 60 minutes prior to the infusion.
-Infuse the diluted CF bag first followed by the diluted NF bag.
Preparation:
NOTE: Follow the preparation steps below for both the CF and NF cryopreserved bags. Thaw the CF first; do not thaw the NF cryopreserved bag until the diluted CF bag has been safely administered.
-Remove from storage and place the Infusion Solution in the Biological Safety Cabinet (BSC) (if available) for 20 minutes to up to 24 hours at room temperature.
-Remove the metal cassette from the liquid nitrogen storage; leave the cryopreserved bag in the overwrap bag during thawing and dilution.
-Once the cryopreserved bag is removed from the metal cassette, thawing and dilution must be carried to completion and the cells administered within 2 hours post-dilution for the CF and within 1 hour post-dilution for the NF.
-After incubating the cryopreserved bag for 5 minutes at room temperature, place it in an approximately 37 degrees C water bath until the product reaches a liquid consistency (usually takes 3 to 8 minutes).
-Do not massage, knead, or apply pressure; keep the bag fully submerged until thawed.
-Remove the thawed bag from the water bath when the cells have completely thawed; do not remove the overwrap bag.
Dilution:
-Remove the Infusion Solution from its sterile bag; ensure that the pinch clamp is closed.
-While it remains in the overwrap bag, insert the spike adapter attached to the Infusion Solution bag into one of the ports of the thawed bag.
CF: Open the pinch clamp on the Infusion Solution tubing and add approximately 20 mL to the CF bag; gently swirl the bag until mixed well. Add the remaining Infusion Solution (approximately 60 mL) to the CF bag; close the valve and swirl gently.
NF: Open the pinch clamp on the Infusion Solution tubing and add approximately 10 mL to the NF bag; gently swirl the bag until mixed well. Add the remaining Infusion Solution (approximately 30 mL) to the NF bag; close the valve and swirl gently.
-Remove the overwrap of the diluted bag and check its integrity; place in a new sterile bag.
Intravenous (IV) Infusion:
-Administer the diluted CF bag first; begin the NF infusion within 1 hour after the end of the CF infusion.
-Prime the infusion set tubing with normal saline prior to spiking the CF or NF bag.
-Administer IV via gravity infusion through a central venous catheter; do not use a leukodepleting filter.
-Infuse the entire contents within 2 hours post-dilution for the CF and within 1 hour post-dilution for the NF; do not exceed an infusion rate of 10 mL/kg per hour.
-Monitor patients for signs and symptoms of infusion-related reactions during the CF infusion. If a reaction occurs, hold the infusion and administer supportive care as needed; appropriately manage the reaction before thawing the NF.
-Following the infusion, wash the tubing with normal saline at the same infusion rate to ensure as many cells as possible are delivered to the patient.
Rare genetic diseases involving the hematopoietic system and infectious diseases may be transmitted in patients who receive an allogenic umbilical cord stem-cell transplant with omidubicel. Report the occurrence of a transmitted infection to Gamida Cell at 844-477-7478. Since March 2016, umbilical cord blood donors are screened for human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), T. pallidum, West Nile Virus (WNV), transmissible spongiform encephalopathy agents, vaccinia, and Zika virus. Maternal blood samples are tested for HIV types 1 and 2, HTLV types I and II, HBV, HCV, T. pallidum, and WNV. Maternal and infant donor blood is also tested for evidence of donor infection due to CMV.
Grade 3 or 4 pain occurred in 33% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Two cases of post-transplant lymphoproliferative disorder (PTLD) and 1 case of donor cell transmitted myelodysplastic syndrome have been reported in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel. Monitor patients life-long for the development of a new primary malignancy. Report the occurrence of a new primary malignancy to Gamida Cell at 844-477-7478. PTLD development may be attributed to donor lymphoid cells transformed by the Epstein-Barr virus (EBV). Consider serial blood monitoring of EBV DNA in patients who have persistent cytopenias.
Graft-versus-host disease (GVHD) has been reported following omidubicel administration. Monitor patients for signs and symptoms of GVHD; treat patients who develop GVHD. Acute (58%; grade 3 or 4, 17%) and chronic (35%) GVHD occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel in a pooled analysis of clinical trials (n = 117). Acute (62%; grade 3 or 4, 15%) and chronic (35%; moderate to severe, 23%) GVHD were reported in patients who received omidubicel (n = 52) in a randomized trial; 6% of patients died from acute GVHD in this trial.
Viral (75%; grade 3, 8%), bacterial (65%; grade 3, 8%), and fungal (21%; grade 3, 6%) infection occurred in who received omidubicel (n = 52) in a randomized trial; 6% of patients died from infection in this trial.
Grade 3 or 4 fatigue including asthenia occurred in 4% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Grade 3 or 4 fever occurred in 2% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Grade 3 or 4 hypertension occurred in 25% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Grade 3 or 4 bleeding occurred in 12% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial; 2% of patients died from a pulmonary hemorrhage in this trial. The term bleeding included hemorrhagic cystitis, epistaxis, GI bleeding, pulmonary alveolar hemorrhage, and subarachnoid hemorrhage.
Grade 3 or 4 gastrointestinal toxicity (19%), dysphagia (12%), and mucosal inflammation (31%) occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.[
Fatal cases of thrombotic thrombocytopenic purpura (TTP)/thrombotic microangiopathy (TMA) were reported in 2% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Nephrotoxicity, specifically increased serum creatinine level (50%; grade 3 or 4, 4%) and grade 3 or 4 renal impairment (12%), occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial. The term renal impairment included acute kidney injury, increased serum creatinine level, and renal failure.
Elevated hepatic enzymes including increased AST or ALT (56%; grade 3 or 4, 13%) and alkaline phosphatase (42%) levels and hyperbilirubinemia (42%; grade 3 or 4, 12%) occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial. Additionally, 2% of patients died from veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) in this trial.
Grade 3 or 4 respiratory failure (12%) and dyspnea (8%) occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial. The term respiratory failure included acute respiratory distress syndrome (ARDS) and hypoxia.
Hypomagnesemia (94%; grade 3 or 4, 4%) and hypermagnesemia (15%; grade 3 or 4, 2%) occurred in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel (n = 52) in a randomized trial.
Infusion-related reactions have been reported with omidubicel. Monitor patients for signs and symptoms of infusion reactions during and after the omidubicel infusion; hold or discontinue the omidubicel infusion depending on the severity of the reaction and institute supportive care as needed. Infusion-related reactions occurred in 47% (grade 3 or 4, 15%) of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel in a pooled analysis of clinical trials (n = 117). Infusion-related reactions were reported in 56% (grade 3 or 4, 17%) of patients who received omidubicel (n = 52) in a randomized trial; common reactions included hypertension, mucosal inflammation, arrythmia, and fatigue.
Primary graft failure (defined as failure to achieve an absolute neutrophil count greater than 500 cells/microliter by day 42 after transplantation) has been reported with omidubicel. Monitor laboratory values for evidence of hematopoietic recovery (e.g., CBC with differential). Primary graft failure occurred in 3% of patients who received an allogenic umbilical cord stem-cell transplant with omidubicel in a pooled analysis of clinical trials (n = 117). Primary graft failure was reported in 2% of patients who received omidubicel (n = 52) in a randomized trial. Additionally, secondary graft failure occurred concurrently with relapsed acute lymphocytic leukemia in 1 patient at approximately 6 months after transplantation.
Engraftment syndrome may occur in patients who receive an allogenic umbilical cord stem-cell transplant with omidubicel. Monitor patients for signs and symptoms of engraftment syndrome such as unexplained fever, rash, hypoxemia, weight gain, and pulmonary infiltrates in the peri-engraftment period. Treat patients who develop engraftment syndrome with corticosteroids to ameliorate symptoms; this syndrome may progress to multiorgan failure and death if left untreated.
Omidubicel use is contraindicated in patients with known dimethyl sulfoxide (DMSO) hypersensitivity, Dextran 40 hypersensitivity, gentamicin aminoglycoside hypersensitivity, albumin hypersensitivity, or bovine protein hypersensitivity. Patients with a history of hypersensitivity to antibiotics should be monitored for allergic reactions following omidubicel administration; it may contain residual antibiotics if the cord blood donor was exposed to antibiotics in utero.
Monitor patients for signs and symptoms of infusion-related reactions (e.g., hypertension, mucosal inflammation, dysphagia, dyspnea, vomiting, and gastrointestinal toxicity) during and after the omidubicel infusion. Symptoms may occur within minutes of starting the infusion and intensify and peak several hours after the infusion. Premedicate patients with acetaminophen, an antihistamine, and hydrocortisone approximately 30 to 60 minutes prior to the infusion. Hold the infusion and institute supportive care as needed if a patient develops an infusion reaction; discontinue omidubicel for severe reactions.
Monitor patients life-long for the development of a new primary malignancy. Post-transplant lymphoproliferative disorder (PTLD) and donor cell transmitted myelodysplastic syndrome have been reported in patients who received an allogenic umbilical cord stem-cell transplant with omidubicel. PTLD development may be attributed to donor lymphoid cells transformed by the Epstein-Barr virus (EBV). Consider serial blood monitoring of EBV DNA in patients who have persistent cytopenias.
Use omidubicel during pregnancy only if the potential benefit justifies the potential risk to the fetus. Verify that pregnancy testing was performed in patients of reproductive potential prior to starting the conditioning regimen. There are no human or animal reproductive data or developmental toxicity studies to assess fetal harm when omidubicel is administered in pregnant patients.
Weigh the developmental and health benefits of breast-feeding with the potential for adverse effects in the breast-fed child from omidubicel or the underlying maternal condition. It is not known if omidubicel is present in human milk or if it has effects on the breastfed infant or milk production.
Monitor for signs and symptoms of graft-versus-host disease (GVHD) in patients who receive an allogenic umbilical cord stem-cell transplant with omidubicel. Administer immunosuppressive drugs (e.g., tacrolimus or cyclosporin plus mycophenolate mofetil) to decrease the risk of GVHD in these patients. Acute GVHD symptoms may include maculopapular rash, gastrointestinal symptoms, and hyperbilirubinemia.
In the peri-engraftment period, monitor patients who receive an allogenic umbilical cord stem-cell transplant with omidubicel for signs and symptoms of engraftment syndrome such as unexplained fever, rash, hypoxemia, weight gain, and pulmonary infiltrates. Treat patients who develop engraftment syndrome with corticosteroids to ameliorate symptoms; engraftment syndrome may progress to multiorgan failure and death if left untreated.
Monitor laboratory values for evidence of hematopoietic recovery (e.g., CBC with differential) in patients who receive an allogenic umbilical cord stem-cell transplant with omidubicel. Primary and secondary graft failure has been reported following omidubicel administration. Immunologic rejection is the primary cause of graft failure.
For use in hematopoietic stem cell transplant following myeloablative conditioning in patients with hematologic malignancies to reduce the time to neutrophil recovery and incidence of infection:
NOTE: The FDA has designated omidubicel as an orphan drug for this indication.
Intravenous dosage:
Adults: Infuse the cultured fraction (minimum dose of 8 X 108 total viable cells containing a minimum of 9.2 X 107 CD34+ cells) followed by the noncultured fraction (minimum dose of 4 X 108 total viable cells containing a minimum of 2.4 X 107 CD3+ cells); this is considered a single dose. Premedicate patients with acetaminophen 650 mg PO, an antihistamine (e.g., diphenhydramine 50 mg IV), and hydrocortisone 50 mg IV starting 30 to 60 minutes prior to the infusion. Ensure the patient is well hydrated. Hold the infusion for hypersensitivity reactions or moderate to severe infusion reactions. The time to neutrophil engraftment (primary endpoint) was significantly improved in patients with hematologic malignancies who received an allogeneic stem cell transplant with omidubicel compared with standard umbilical cord blood (UCB) (12 days vs. 22 days; p less than 0.001) in a multicenter, randomized, phase 3 trial (n = 125; Study P0501). Additionally, the rate of platelet engraftment by 42 days was significantly higher in omidubicel-treated patients (55% vs. 35%; p = 0.028). The incidence of grade 2 or 3 bacterial or invasive fungal infection within the first 100 days after transplant was 37% in the omidubicel arm and 57% in the standard UCB arm (p = 0.03). Graft-versus-host disease (GVHD) rates, treatment failure rates, and mortality rates were not significantly different between treatment arms. Of note, patients treated with omidubicel received a transplant at a median of 41 days after random assignment compared with 26 days for patients treated with standard UCB. Eligible patients (median age, 41 years; range, 13 to 65 years) had at least a 4 of 6 human leukocyte antigen (HLA) donor match. Conditioning regimens included total body irradiation and fludarabine plus thiotepa or cyclophosphamide or chemotherapy only with thiotepa, busulfan, and fludarabine. All patients received GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil; antibacterial prophylaxis and granulocyte-colony stimulating factors were given post transplant.
Children and Adolescents 12 years and older: Infuse the cultured fraction (minimum dose of 8 X 108 total viable cells containing a minimum of 9.2 X 107 CD34+ cells) followed by the noncultured fraction (minimum dose of 4 X 108 total viable cells containing a minimum of 2.4 X 107 CD3+ cells); this is considered a single dose. Premedicate patients with acetaminophen 10 mg/kg (maximum of 650 mg) PO, an IV antihistamine (e.g., diphenhydramine 0.5 mg/kg up to a maximum of 50 mg), and hydrocortisone 0.5 mg/kg (maximum of 50 mg) IV starting 30 to 60 minutes prior to the infusion. Ensure the patient is well hydrated. Hold the infusion for hypersensitivity reactions or moderate to severe infusion reactions. The time to neutrophil engraftment (primary endpoint) was significantly improved in patients with hematologic malignancies who received an allogeneic stem cell transplant with omidubicel compared with standard umbilical cord blood (UCB) (12 days vs. 22 days; p less than 0.001) in a multicenter, randomized, phase 3 trial (n = 125; Study P0501). Additionally, the rate of platelet engraftment by 42 days was significantly higher in omidubicel-treated patients (55% vs. 35%; p = 0.028). The incidence of grade 2 or 3 bacterial or invasive fungal infection within the first 100 days after transplant was 37% in the omidubicel arm and 57% in the standard UCB arm (p = 0.03). Graft-versus-host disease (GVHD) rates, treatment failure rates, and mortality rates were not significantly different between treatment arms. Of note, patients treated with omidubicel received a transplant at a median of 41 days after random assignment compared with 26 days for patients treated with standard UCB. Eligible patients (median age, 41 years; range, 13 to 65 years) had at least a 4 of 6 human leukocyte antigen (HLA) match. Conditioning regimens included total body irradiation and fludarabine plus thiotepa or cyclophosphamide or chemotherapy only with thiotepa, busulfan, and fludarabine. All patients received GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil; antibacterial prophylaxis and granulocyte-colony stimulating factors were given post transplant.
Maximum Dosage Limits:
-Adults
The maximum dose has not been determined; up to 39 X 108 CD34+ cells were infused following cell expansion in a clinical trial.
-Geriatric
The maximum dose has not been determined; up to 39 X 108 CD34+ cells were infused following cell expansion in a clinical trial.
-Adolescents
The maximum dose has not been determined; up to 39 X 108 CD34+ cells were infused following cell expansion in a clinical trial.
-Children
12 years: The maximum dose has not been determined; up to 39 X 108 CD34+ cells were infused following cell expansion in a clinical trial.
Less than 12 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Anticoagulants: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Antithrombin III: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Apixaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Argatroban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Betrixaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Bivalirudin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dabigatran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dalteparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Edoxaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Enoxaparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Fondaparinux: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Heparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Pentosan: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Rivaroxaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Warfarin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Omidubicel is a cryopreserved nicotinamide (NAM)-modified allogeneic hematopoietic progenitor cell therapy derived from the same patient-specific cord blood unit. It consists of 2 components: 1) a Cultured Fraction (CF) of allogeneic, CD34+ hematopoietic progenitor cells (HPCs) and differentiated myelomonocytic cells, dendritic cells, and granulocytes and 2) a Noncultured Fraction of allogeneic, hematopoietic mature myeloid and lymphoid cells and other lineage committed hematopoietic cells. Ex-vivo culturing of cord blood derived HPCs in the presence of NAM helps to preserve their stemness and prevent the accelerated proliferation, differentiation, cellular stress, and signaling pathways that typically happens when HPCs are removed from the cord. NAM-modified HPCs migrate to the bone marrow and result in rapid neutrophil engraftment and multi lineage immune reconstitution.
Omidubicel is administered intravenously. Rapid and broad immune reconstitution of dendritic cells, monocytes, natural killer (NK) cells, CD4+ T cells, and CD8+ T cells occur as soon as 1 week post transplantation. B-cell reconstitution occurs as early as 28 days post transplantation and all lineage cell reconstitution occurs throughout the 1-year follow-up period. There is a linear correlation between the CD34+ cell content in the Culture Fraction and the reconstitution of T-cells and NK cells. Additionally, days to neutrophil recovery decreased with an increase in the omidubicel CD34+ cell dose in dose-response modeling.