Denileukin Diftitox

Denileukin diftitox-cxdl is a fusion protein designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death.

• LYMPHIR is indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.ICD-10: C85.90

• None. None.contraindicated

Delay start of treatment cycle if serum albumin level is below 3 g/dL. ( 2.1 ) The recommended dosage of LYMPHIR is 9 mcg/kg/day actual body weight administered as an intravenous infusion on Days 1 through 5 of a 21-day cycle. ( 2.2 ) Administer premedication as recommended. ( 2.3 ) See full prescribing information for preparation and administration instructions. ( 2.5 ) 2.1 Important Dosing Instructions Prior to starting each treatment cycle, assess hepatic and renal function. If serum albumin is less than 3 g/dL, delay administration of LYMPHIR until serum albumin is greater than or equal to 3 g/dL [see Warnings and Precautions ( 5.1 )] . 2.2 Recommended Dosage The recommended dosage of LYMPHIR is 9 mcg/kg/day actual body weight administered as an intravenous infusion over 60 minutes on Days 1 through 5 of a 21-day treatment cycle. Administer LYMPHIR until disease progression or unacceptable toxicity. 2.3 Recommended Premedications Administer premedications prior to starting a LYMPHIR infusion in Cycles 1 through 3, as outlined in Table 1, to reduce the risk of infusion-related reactions [see Warnings and Precautions ( 5.3 )] . Table 1.

Visual Impairment: Monitor and evaluate for visual impairment throughout treatment. Withhold LYMPHIR until visual impairment resolves or permanently discontinue based on severity. ( 5.2 ) Infusion-Related Reactions: Monitor patients closely during infusions. Interrupt or discontinue for infusion-related reactions based on severity. ( 5.3 ) Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. ( 5.4 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Capillary Leak Syndrome LYMPHIR can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as capillary leak syndrome. As defined, CLS occurred in 27% of patients in the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution. The most common symptoms included edema, hypoalbuminemia, and hypotension.

The following adverse reactions are discussed in greater detail in other sections of the label: Capillary Leak Syndrome [see Warnings and Precautions ( 5.1 )] Visual Impairment [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Citius Oncology, Inc. at 1-844-459-6744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LYMPHIR as a single agent in 119 patients with CTCL across 3 clinical trials. Patients received treatment with LYMPHIR as an intravenous infusion at 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle until disease progression or unacceptable toxicity. Among 119 patients who received LYMPHIR the median number of cycles received was 5 (range: 1 to 42), with 13% exposed for 6 months or longer.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox. Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. 8. 2 Lactation Risk Summary No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose. 8.3 Females and Males of Reproductive Potential Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] .

Metabolism

12. 3 Pharmacokinetics Following a single dose of denileukin diftitox-cxdl 9 mcg/kg via 1-hr infusion on Cycle 1, Day 1 in patients with CTCL, the geometric mean (coefficient of variation [CV]%) maximum serum concentration (C max ) was 94.4 ng/mL (77%) and area under the concentration over time curve (AUC 0-inf ) was 20700 ng· min/L (60%).

• Aug 7, 2024BLABLA761312Citius Pharms

1. 1Capillary Leak Syndrome125%
2. 2Cognitive Disorder125%
3. 3Communication Disorder125%
4. 4Death125%
5. 5Disease Progression125%
6. 6Hypoxia125%
7. 7Oxygen Saturation Decreased125%
8. 8Rash125%
9. 9Sepsis125%

The 10 most recently updated of 50 ClinicalTrials.gov registrations naming Denileukin Diftitox as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• T-regulatory Cell Depletion With E7777 Combined With Pembrolizumab in Recurrent or Metastatic Solid Tumors
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 25 enrolled · Alexander B Olawaiye, MD
  NCT05200559updated 2026-05-29
• A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel
  Recruiting · Phase 1 · Phase 2 · Interventional · 42 enrolled · Iovance Biotherapeutics, Inc.
  NCT06940739updated 2025-12-03
• HCW9302 (Interleukin-2 Fusion Protein) for Alopecia Areata
  Recruiting · Phase 1 · Interventional · 30 enrolled · HCW Biologics
  NCT07049328updated 2025-10-20
• A Study of Remitoro in Participants With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study)
  Completed · Observational · 118 enrolled · Eisai Inc.
  NCT05137847updated 2023-12-12
• Denileukin Diftitox in Treating Patients With Non-Hodgkin's Lymphoma
  Completed · Phase 2 · Interventional · 77 enrolled · Eastern Cooperative Oncology Group
  NCT00003615updated 2023-06-15
• Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage III-IV Melanoma
  Terminated · Phase 1 · Phase 2 · Interventional · 3 enrolled · Fred Hutchinson Cancer Center
  NCT00945269updated 2022-11-15
• Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma
  Completed · Phase 2 · Interventional · 75 enrolled · Eisai Inc.
  NCT01127451updated 2022-04-13
• Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
  Completed · Phase 2 · Interventional · 180 enrolled · National Heart, Lung, and Blood Institute (NHLBI)
  NCT00224874updated 2021-11-01
• Ipilimumab Administered to Stage IIIC Stage IV Melanoma After Reg. T Cell Depletion With Denileukin Diftitox
  Terminated · Phase 2 · Interventional · 2 enrolled · University of Louisville
  NCT02009384updated 2021-10-25
• Vaccination Plus Ontak in Patients With Metastatic Melanoma
  Terminated · Phase 2 · Interventional · 17 enrolled · University of Chicago
  NCT00515528updated 2021-01-26

Frequently asked questions

How does Denileukin Diftitox work?

Denileukin diftitox-cxdl is a fusion protein designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death.

What is Denileukin Diftitox used for?

According to FDA labeling, Denileukin Diftitox carries indications including: LYMPHIR is indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Denileukin Diftitox?

Denileukin Diftitox is classified as Other antineoplastic agents, CD25-directed Cytotoxin.

What are the brand names for Denileukin Diftitox?

Denileukin Diftitox is marketed under brand names including Lymphir.

What are the contraindications for Denileukin Diftitox?

Denileukin Diftitox labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.