Treosulfan

• GRAFAPEX is an alkylating drug indicated for: Use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML). ( 1.1 ).ICD-10: C95.90

• GRAFAPEX is contraindicated in patients with hypersensitivity to any component of the drug product. Hypersensitivity to any component of the drug product.contraindicated

Recommended dosage: 10 g/m² body surface area (BSA) per day as a two hour intravenous infusion, given on three consecutive days (day -4, -3, -2) in conjunction with fludarabine before hematopoietic stem cell infusion (day 0). ( 2.1 , 2.2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of GRAFAPEX is 10 g/m 2 by intravenous infusion given daily for three days, beginning on Day -4 prior to transplantation in combination with fludarabine as outlined in Table 1. Table 1: Dosage Regimen for GRAFAPEX-Based Allogeneic HSCT Treatment Day -6 Day -5 Day -4 Day-3 Day -2 Day -1 Day 0 GRAFAPEX 10 g/m 2 /day intravenous infusion X X X Fludarabine 30 mg/m 2 /day intravenous infusion X X X X X Allogeneic hematopoietic stem cell infusion X Premedicate patients with antiemetics prior to the first dose of GRAFAPEX and continue antiemetics on a fixed schedule through completion of treosulfan administration. 2.2 Preparation and Administration Instructions Reconstitute GRAFAPEX prior to intravenous infusion. GRAFAPEX is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Use aseptic technique to prepare GRAFAPEX. Calculate the dose, the total volume of reconstituted GRAFAPEX solution required, and the number of GRAFAPEX vials needed.

Seizures: Monitor signs of neurological adverse reactions and consider clonazepam prophylaxis for patients at higher risk. ( 5.2 ) Skin disorders: Keep skin clean and dry on days of GRAFAPEX infusion and change occlusive dressings after infusion. Change diapers frequently during the 12 hours after each infusion of GRAFAPEX. ( 5.3 ) Injection Site Reactions and Tissue Necrosis: May cause local tissue necrosis and injection site reactions, including erythema, pain, and swelling, in case of extravasation. If extravasation occurs, stop the infusion immediately and manage medically as required. ( 5.4 ) Secondary Malignancies: There is an increased risk of a secondary malignancy with use of GRAFAPEX. ( 5.5 ) Increased Early Morbidity and Mortality at Dosages Higher than Recommended: Avoid exceeding the recommended dosage of 10 g/m 2 daily for three consecutive days. ( 5.6 ) Embryo-fetal toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Myelosuppression Profound myelosuppression with pancytopenia is the desired therapeutic effect of GRAFAPEX-based preparative regimens, occurring in all patients. Time to neutrophil counts > 0.5 Gi/L occurred at a median of 18 days (range 7-42 days) after allogeneic hematopoietic stem cell transplantation in adult patients treated using GRAFAPEX in combination with fludarabine as the preparative regimen. Do not begin the preparative regimen if the stem cell donor is not available.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions ( 5.1 )] Seizures [see Warnings and Precautions ( 5.2 )] Skin Disorders [see Warnings and Precautions ( 5.3 )] Injection Site Reactions and Tissue Necrosis [see Warnings and Precautions ( 5.4 )] Secondary Malignancies [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (≥20%) are musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. ( 6.1 ) Selected Grade 3 or 4 nonhematological laboratory abnormalities are increased GGT, increased bilirubin, increased ALT, increased AST, and increased creatinine. To report SUSPECTED ADVERSE REACTIONS, contact Medexus Pharma, Inc. at 1-855-336 -3322 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. MC‑FludT.14/L Trial II The safety of GRAFAPEX was evaluated in 553 adult patients with AML and MDS in a randomized trial (MC‑FludT.14/L Trial II) comparing GRAFAPEX in combination with fludarabine to busulfan in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, GRAFAPEX can cause fetal harm when administered to a pregnant woman because it is genotoxic and affects dividing cells [see Clinical Pharmacology ( 12 ) and Nonclinical Toxicology ( 13 )] . There are no available human clinical data on the use of treosulfan in pregnant women to support an estimation of a drug-associated risk. Specific embryo-fetal developmental toxicity studies with treosulfan in animals were not conducted. Advise pregnant women of the potential risk to a fetus [see Data]. In the U.S. general population, the estimated background risk of major birth defects is 2% – 4% and of miscarriage is 15% – 20% of clinically recognized pregnancies. Data Animal Data Animal reproductive or developmental toxicity studies were not conducted with treosulfan. Treosulfan is genotoxic and is toxic to dividing cells, suggesting it can cause embryotoxicity and teratogenicity. 8.2 Lactation Risk Summary There is no data on the presence of treosulfan or its metabolites 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 GRAFAPEX and for 1 week after the last dose.

The principal toxic effect of treosulfan in cases of overdose are myeloablation and prolonged pancytopenia, mucositis, skin toxicity, nausea, vomiting and gastritis. In case of overdosage, monitor blood counts frequently and provide vigorous supportive measures as medically indicated.

• Jan 21, 2025NDANDA214759Medexus

1. 1Off Label Use59624%
2. 2Cytomegalovirus Infection25910%
3. 3Cytomegalovirus Infection Reactivation2469.8%
4. 4Mucosal Inflammation2339.2%
5. 5Drug Ineffective2279.0%
6. 6Product Use In Unapproved Indication2258.9%
7. 7Adenovirus Infection2048.1%
8. 8Acute Graft Versus Host Disease In Skin1987.8%
9. 9Graft Versus Host Disease In Skin1455.7%
10. 10Acute Graft Versus Host Disease1265.0%
11. 11Pyrexia1265.0%
12. 12Graft Versus Host Disease In Gastrointestinal Tract1234.9%
13. 13Multiple Organ Dysfunction Syndrome1224.8%
14. 14Human Herpesvirus 6 Infection1194.7%
15. 15Neutropenia1164.6%

The 10 most recently updated of 56 ClinicalTrials.gov registrations naming Treosulfan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
  Recruiting · Phase 2 · Interventional · 60 enrolled · Fred Hutchinson Cancer Center
  NCT04195633updated 2026-05-29
• FLUDARABINE-TREOSULFAN REDUCED INTENSITY CONDITIONING REGIMEN PRIOR HAPLOIDENTICAL STEM CELL TRANSPLANTATION WITH POST TRANSPLANTATION CYCLOPHOSPHAMIDE FOR OLDER AND/OR FRAIL PATIENTS WITH AML
  Not yet recruiting · Phase 2 · Interventional · 77 enrolled · Institut Paoli-Calmettes
  NCT07598110updated 2026-05-20
• Effect of Moderate Renal Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics
  Completed · Phase 1 · Interventional · 20 enrolled · medac GmbH
  NCT05534620updated 2026-05-20
• Phase III Study Comparing GVHD Prophylaxis With ATG-thymoglobulin to ATLG-grafalon in Elderly Patients With Acute Myeloid Leukemia or Myelodysplasic Syndrome and Receiving an Allogeneic Hematopoietic Stem Cell Transplantation With a 10/10 HLA Matched Unrelated Donor
  Recruiting · Phase 3 · Interventional · 324 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT06083129updated 2026-04-27
• Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients
  Recruiting · Observational · 70 enrolled · Fondazione IRCCS Policlinico San Matteo di Pavia
  NCT06861257updated 2026-04-24
• MT2025-35 Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning Treosulfan and Fludarabine, With Post-Transplant Cytoxan (PTCy) for the Treatment of Hematological Diseases
  Recruiting · Phase 2 · Interventional · 132 enrolled · Masonic Cancer Center, University of Minnesota
  NCT07493538updated 2026-04-16
• Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders
  Recruiting · Phase 2 · Interventional · 40 enrolled · Fred Hutchinson Cancer Center
  NCT03980769updated 2026-03-12
• Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
  Completed · Phase 2 · Interventional · 40 enrolled · Fred Hutchinson Cancer Center
  NCT04965597updated 2026-03-09
• Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia
  Active not recruiting · Phase 2 · Interventional · 23 enrolled · Fred Hutchinson Cancer Center
  NCT04994808updated 2026-01-26
• Study of Treosulfan-Based Conditioning for HSCT in Nijmegen Breakage Syndrome
  Not yet recruiting · Phase 2 · Interventional · 24 enrolled · Federal Research Institute of Pediatric Hematology, Oncology and Immunology
  NCT07316595updated 2026-01-05

Frequently asked questions

What is Treosulfan used for?

According to FDA labeling, Treosulfan carries indications including: GRAFAPEX is an alkylating drug indicated for: Use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML). ( 1.1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Treosulfan?

Treosulfan is classified as Alkyl sulfonates.

What are the brand names for Treosulfan?

Treosulfan is marketed under brand names including Grafapex.

What are the contraindications for Treosulfan?

Treosulfan labeling lists contraindications including: GRAFAPEX is contraindicated in patients with hypersensitivity to any component of the drug product. Hypersensitivity to any component of the drug product.. Always consult the full prescribing information and a clinician.