Kepivance (palifermin) / SOBI, Amgen - LARVOL DELTA

Addition of Myeloablative Doses of Total Marrow Irradiation (TMI) to Myeloablative Fludarabine/Busulfan Conditioning for Allogeneic HSCT in Patients with High-Risk AML, CML, or Myelodysplastic Syndrome: A Phase II Clinical Trial (ASH 2023) - P2 | "The study included patients with matched related donors (MRD, n=9) receiving TMI/FluBu4 as a preparative regimen and patients with matched unrelated (MUD, n=13) or 1-antigen mismatched unrelated (MMUD, n=6) donors receiving conditioning with TMI/FluBu4 + rabbit anti-thymocyte globulin (rATG). Graft-versus-host disease (GVHD) prophylaxis was with methotrexate and tacrolimus, and palifermin was used to prevent severe mucositis...Kaplan Meyer curves for Overall Survival (OS) and DFS are shown in Figure 1 and 2, respectively. Addition of myeloablative TMI at 9Gy to standard myeloablative targeted FluBu4 was well tolerated and achieved very encouraging results in a group of patients with myeloid malignancies at high risk of relapse (clinicaltrials.gov Identifier: NCT03121014)."

Clinical • P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Transplantation

Preconditioning Single High-Dose Palifermin Alters the Posttransplant Inflammatory Cytokine Profile (ASH 2023) - P1/2, P2 | "This trial evaluates the incidence of severe CGVHD (primary objective of phase 2) following the addition of a single high dose of palifermin to GVHD prophylaxis with TMS (tacrolimus, methotrexate, sirolimus)...All patients received cyclophosphamide (total 4.8 g/m2) and fludarabine (total 120 mg/m2) as conditioning on days −6 to −3 followed by infusion of an 8/8 HLA-matched unrelated donor peripheral blood cell graft on day 0...Further investigations focusing on GI microbiome and immune cell subsets are needed to elucidate the consequences of cytokine alterations induced by KGF on immune cell reconstitution. This research was supported by the Intramural Research Program of the NIH, NCI, CCR."

Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Mucositis • Stomatitis • Transplantation • CD4 • CD8 • CXCL9 • IL12A • IL15 • IL22 • IL7 • TNFA

Comparison of Two Myeloablative Total-Body Irradiation (MAC-TBI) Regimens: 1200 Cgy Vs 800 Cgy of TBI for Allogeneic Stem Cell Transplantation in Adults with Hematological Malignancies (ASH 2024) - "The Fine-Gray model was used to correlate acute graft-versus-host disease (aGVHD) with clinical factors.Results : Twelve patients (52.2%) received fludarabine and TBI800, 9 patients (39.1%) received cyclophosphamide (Cy) and TBI1200, and 2 patients (8.7%) received fludarabine and TBI 1200 cGy. GVHD prophylaxis included : post-transplant Cy, mycophenolate mofetil, and tacrolimus in 5 patients (21.7%) and methotrexate and tacrolimus in 18 patients (78.3%). Palifermin was administered to 43.5% patients (25% in the TBI800 group vs 63.6% in the TBI1200 group, p=0.1)...The Multivariable Fine-Gray Model showed a higher risk of aGVHD, particularly grade I-II, in the TBI1200 group (HR 6.66, 95% CI : 2.07-21.38).Conclusion : TBI800 vs TBI1200 led to similar relapse incidence, with a lower risk of aGVHD and decreased grade 3-4 mucositis rate in the TBI800 group. Studies on a larger scale are required to establish the safety and efficacy of TBI800."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cataract • Dermatitis • Dermatology • Diabetes • Dyslipidemia • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Neutropenia • Novel Coronavirus Disease • Oncology • Ophthalmology • Osteoporosis • Respiratory Diseases • Rheumatology • Transplantation

Salivary gland tissue chip screening identifies candidate radioprotective drugs. (PubMed, Commun Med (Lond)) - "This body of work demonstrates the development and validation of assays using a tissue chip platform for high-content drug screening and the successful discovery and in vivo validation of candidate radioprotective drugs with non-antioxidant primary modes of action. These results point to possible unknown mechanisms of radioprotection. These drugs can be developed to improve radioprotection efficacy and clinical administration without adverse side-effects."

Journal • Dental Disorders • Head and Neck Cancer • Infectious Disease • Oncology • Solid Tumor • Xerostomia

Efficacy of Treatment and Prevention of Radiation-induced Oral Mucositis- Systematic Review (AAO-HNSF 2025) - "Review of these papers papers supports good oral care, IMRT, radiation shields, palifermin, and amifostine. To our knowledge, this study represents the largest review of RIOM. It is limited by the diversity of study designs, sample sizes, patient characteristics, and outcome measures. While there is no objectively universal treatment for RIOM, preliminary results from this review show promise with multiple therapies."

Clinical • Review • Head and Neck Cancer • Mucositis • Oncology • Stomatitis

Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Suspended ➔ Recruiting

Enrollment open • Immunology • Primary Immunodeficiency

Base Editing Hematopoietic Stem Cell and T Cell Gene Therapy for CD40L-HyperIgM Syndrome: Single Patient Study (clinicaltrials.gov) - P1/2 | N=1 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Enrolling by invitation ➔ Recruiting

Enrollment status • Gene Therapies • Immunology • Primary Immunodeficiency • CD40LG

Addressing Pain in Oral Mucositis: Narrative Review of Current Practices and Emerging Treatments. (PubMed, J Pain Res) - "Given the debilitating nature of OM in cancer patients and the critical need for effective pain control, this review aims to examine pharmacological advancements targeting the complex nature of OM-related pain, including agents such as lidocaine, doxepin, benzydamine, methylene blue, opioids, gabapentin, palifermin, caphosol, and ketamine...This review highlights the clinical applicability of emerging therapies, such as avasopasem manganese, which has demonstrated efficacy in mitigating OM progression...Addressing the multifaceted nature of OM-associated pain is essential for enhancing quality of life and optimizing cancer treatment outcomes. Further research is needed to establish robust, evidence-based guidelines for OM pain management."

Journal • Review • Bone Marrow Transplantation • Head and Neck Cancer • Infectious Disease • Mucositis • Oncology • Oral Cancer • Pain • Solid Tumor • Stomatitis • Transplantation

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan, and Total Marrow and Lymphoid Irradiation for the Treatment of High-Risk Acute Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting | N=12 ➔ 7

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FLT3 • IL2RA • ISG20 • NPM1

Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1/2 | N=34 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Dec 2027 ➔ Mar 2025

Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • ABL1 • ASXL1 • BCR • CD34 • FLT3 • HLA-B • HLA-C

Human Lysozyme Goat Milk for the Prevention of Graft Versus Host Disease in Patients With Blood Cancer Undergoing a Donor Stem Cell Transplant (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation • HLA-DRB1

Phase 1b/2a Trial of Allogeneic HSCT From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset Medically Refractory Crohn Disease (clinicaltrials.gov) - P1/2 | N=14 | Not yet recruiting | Sponsor: Stanford University

New P1/2 trial • Bone Marrow Transplantation • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Transplantation

Base Editing Hematopoietic Stem Cell Gene Therapy for CD40L-HyperIgM Syndrome: Single Patient Study (clinicaltrials.gov) - P1/2 | N=1 | Enrolling by invitation | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1/2 trial • Gene Therapies • Immunology • Primary Immunodeficiency • CD40LG

Phase 1/2 Study of High-Dose Palifermin for GVHD Prophylaxis in Patients Undergoing HLA-Matched Unrelated Donor HCT. (PubMed, Blood) - P1/2 | "All 31 patients received fludarabine/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. These findings indicate high-dose palifermin with RIC is safe and may prevent acute GVHD, though it did not impact chronic GVHD rates in this study. NCT02356159."

Journal • P1/2 data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • CD4

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy (clinicaltrials.gov) - P1/2 | N=18 | Enrolling by invitation | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Gene Therapies • Genetic Disorders • Immunology • Primary Immunodeficiency

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2032 ➔ Dec 2034 | Trial primary completion date: Dec 2032 ➔ Dec 2034

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Immunology • Primary Immunodeficiency

Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=1 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=10 ➔ 1

Enrollment change • Immunology • Primary Immunodeficiency

UKALL14: Standard Chemotherapy with or Without Nelarabine or Rituximab in Treating Patients with Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A | N=0 | Completed | Sponsor: University College, London | Active, not recruiting ➔ Completed | N=1033 ➔ 0 | Trial completion date: Dec 2025 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mucositis • Oncology • Stomatitis • ABL1 • BCR • MYC

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1/2 trial • Gene Therapies • Genetic Disorders • Immunology • Primary Immunodeficiency • IL2RG

Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=10 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Suspended

Trial suspension • Immunology • Primary Immunodeficiency • CD34

Human Lysozyme Goat Milk for the Prevention of Graft Versus Host Disease in Patients With Blood Cancer Undergoing a Donor Stem Cell Transplant (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Oct 2025 | Trial primary completion date: Dec 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation • HLA-DRB1

Diagnostic Approaches for Hematopoietic Cell Transplantation Associated Membranous Nephropathy (TCT-ASTCT-CIBMTR 2025) - P1/2 | "All 3 patients were males who received non-myeloablative HCT between 2017-2018, conditioned with fludarabine/cyclophosphamide in combination with a single high dose palifermin prior to chemotherapy (NCT02356159). They received a peripheral blood graft from a matched unrelated donor (1/3 female) with tacrolimus/sirolimus/methotrexate GVHD prophylaxis...All patients were treated with rituximab and prednisone for MN...Large, multi-center collaborative studies are needed to identify additional candidate AGs in post-HCT MN that are negative for FAT1 or other common MN AGs. Such studies will better characterize the incidence, risk factors, clinicopathologic features, underlying mechanisms, response to therapy and outcomes in these distinct MN subsets."

Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Glomerulonephritis • Graft versus Host Disease • Immunology • Renal Disease • Transplantation • CDH23 • EGF • FAT1 • NELL1 • PCDH

Managing strategies of chemotherapy and radiotherapy-induced oral mucositis. (PubMed, Cancer Treat Rev) - "For example, clinical trials assessing established drugs such as melatonin, clonidine, and pentoxifylline indicate promising potential for managing OM. Besides, Verbascoside, Palifermin, Amifostine, and Avasopasem manganese can be suggested for OM management, while the side effects should be monitored. The accessibility and cost/effectiveness of specific managing strategies of OM should be considered when selecting appropriate options."

Clinical • Journal • Review • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis

Palifermin With Leuprolide Acetate for the Promotion of Immune Recovery Following Total Body Irradiation Based T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=82 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD34 • CD4

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan, and Total Marrow and Lymphoid Irradiation for the Treatment of High-Risk Acute Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Jun 2027

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FLT3 • IL2RA • ISG20 • NPM1