Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation
A Phase I/II Open Label, Dose Escalation Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation
2 other identifiers
interventional
34
1 country
2
Brief Summary
Background: \- In allogeneic stem cell transplantation (SCT), stem cells are taken from a donor and given to a recipient. Sometimes the recipient's immune system destroys the donors' cells. Or donor immune cells attack the recipient's tissues, called graft-versus-host disease (GVHD). This is less likely when the recipient and donor have similar human leukocyte antigens (HLA). Researchers want to see if the drug palifermin improves the results of allogeneic SCT from HLA-matched unrelated donors. Objective: \- To see if high doses of palifermin before chemotherapy are safe, prevent chronic GVHD, and improve immune function after transplant. Eligibility: \- Adults 18 years of age or older with blood or bone marrow cancer with no HLA-matched sibling donor, but with a HLA-matched unrelated donor. Description of Research Study:
- Participants will be screened with medical history, physical exam, and blood and urine tests. They will have scans and heart and lung exams.
- Before transplant, participants will:
- Have many tests and exams. These include blood tests throughout the study and bone marrow biopsy.
- Get a central line catheter if they do not have one.
- Have 1-3 rounds of chemotherapy.
- Have more tests to make sure they can have the transplant, including medical history, physical exam, blood tests, disease specific restaging.
- Get palifermin by intravenous (IV) and conditioning chemotherapy to prepare for hematopoietic stem cell transplantation (HSCT). They will get other drugs; some they will take at least 6 months.
- Participants will get the HSCT.
- After transplant, participants will:
- Be hospitalized at least 3-4 weeks.
- Monitored at least weekly for the first 100 days.
- Stay near District of Columbia (D.C). for approximately 100 days post-transplant.
- After 100 days post-transplant - visit National Institutes of Health (NIH) 5 times the first 2 years, then yearly until 5 years post-transplant.
- Additional tests/procedures may be performed to monitor safety, response to transplant, side effects.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2015
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2015
CompletedFirst Posted
Study publicly available on registry
February 5, 2015
CompletedStudy Start
First participant enrolled
September 24, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 25, 2025
CompletedResults Posted
Study results publicly available
June 5, 2025
CompletedSeptember 30, 2025
September 1, 2025
9.2 years
February 4, 2015
April 10, 2025
September 11, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase II: Estimated Percent of Participants Who Experienced Severe Chronic Graft Versus Host Disease (GVHD)
The estimated percent of participants who experienced severe chronic graft versus host disease (GVHD) was assessed by the 1994 Consensus Conference Working Criteria. Severe GVHD is defined using the Global Staging per 2014 National Institutes of Health (NIH) Consensus Criteria for chronic GVHD.
60 months
Phase I: Maximum Tolerated Dose (MTD) of Palifermin
MTD is defined as the dose level at which no more than 1 (of ≤ 6) participants who experience dose-limiting toxicity (DLT), and the dose below that at which at least 2 (of ≤ 6) participants have a DLT as a result of the drug. A DLT is non-relapse mortality before day 30 post transplantation regardless of attribution to palifermin. and non-hematologic grade 4 (life-threatening) adverse events within 14 days after treatment with palifermin possibly related to drug.
Approximately 30-day post-transplant
Phase 1: Number of Participants With a Dose-limiting Toxicity (DLT)
A DLT is non-relapse mortality before day 30 post transplantation regardless of attribution to palifermin. Persons who expire from malignancy related causes are not considered DLTs; and non-hematologic Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 4 adverse events (AEs), occurring within 14 days after administration of palifermin that are determined by the investigator to be at least possibly related to the study drug. An isolated laboratory value is not considered an AE unless it meets the guidelines. Note: Participants will not be removed from study therapy due to palifermin toxicity as only 1 dose is administered. DLT criteria are established only to determine dose levels for subsequent participants.
≤day 30 post-transplant
Other Outcomes (1)
Phase I and/or Phase 2: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
All adverse events, including clinically significant abnormal findings on laboratory evaluations, regardless of severity, will be followed until return to baseline or stabilization of event, up to 5 years.
Study Arms (2)
1/Phase 1: Dose Escalation Arm - Palifermin
EXPERIMENTALInduction chemotherapy, then palifermin at escalating doses, then conditioning chemotherapy, then allogeneic stem cell transplant, then immunosuppression.
2/Phase II Arm - Palifermin at the Recommended Phase 2 Dose
EXPERIMENTALInduction chemotherapy, then palifermin at the recommended phase 2 dose determined in Phase 1, then conditioning chemotherapy, then allogeneic stem cell transplant, then immunosuppression.
Interventions
Rituximab: 375 mg/m\^2 intravenous (IV) day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.
Fludarabine:30 mg/m\^2 per day intravenous (IV) infusion over 30 minutes, daily on days -6, -5, -4, and -3; Cyclophosphamide:1200 mg/m\^2 per day IV infusion over 2 hours on Days 6, -5, -4, -3. Mesna: 1200 mg/m\^2 per day IV infusion, daily on days 6, -5, -4, and -3 Furosemide: 20 mg IV flat dose on days -6, -5, -4, -3; Furosemide: 20 mg IV flat dose on days -6, -5, -4, -3.
Tacrolimus: 0.02 mg/kg, start day 3. Continue intravenous (IV) or by mouth (PO). Taper will begin at day +60 if no acute graft-versus-host disease (GVHD) then at day +100 and discontinue at day +180 as tolerated. Methotrexate: 5 mg/m\^2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 60, followed by a taper if GVHD does not develop.
Fludarabine: 25 mg/m\^2 per day intravenous (IV) over 30 minutes, daily on days 1-5 Cytarabine: 2,000 mg/m\^2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy.
Fludarabine: 25 mg/m\^2 per day intravenous (IV) infusion over 30 minutes, daily on days 1-4. Etoposide: 50 mg/m\^2 per day continuous IV infusion over 24 hours on days 1-4. Doxorubicin: 10 mg/m\^2/day continuous intravenous (CIV), days 1-4. Vincristine: 0.4 mg/m\^2 per day continuous IV infusion over 24 hours daily on days 1-4. Cyclophosphamide: 750 mg/m\^2 IV infusion over 30 minutes on day 5. Prednisone: 60 mg/m\^2 per day by mouth (PO) daily on days 1-5. Filgrastim: 5 mcg/kg per day SC or IV.
Hematopoietic stem cell transplant
Escalating doses of palifermin given during transplant phase.
Before each infusion of rituximab as indicated.
Before each infusion of rituximab as indicated.
For engraftment syndrome.
Emergency medication as indicated.
Before each infusion of rituximab as indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
As indicated.
Eligibility Criteria
You may qualify if:
- Patients meeting below eligibility criteria are eligible to receive suitable disease specific therapy for the purposes of disease control while the donor search takes place
- The patient is greater than or equal to 18 years of age.
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Karnofsky performance score \>= 60.
- No suitable HLA matched sibling donor is available, and the patient has one or more potentially suitable HLA matched unrelated donor(s) in the National Marrow Donor Registry or other available registry.
- The evaluation of donors shall be in accordance with existing National Marrow Donor Program (NMDP) Standard Policies and Procedures
- HLA-matched donors are defined by allele matching at HLA-A, -B, -C,
- There is a high likelihood that the patient, in the opinion of the principal investigator (PI) or lead associate investigator (LAI), will meet the research phase eligibility criteria and proceed to transplant after induction phase therapy is completed.
- Diagnosis of hematologic malignancy meeting at least one of the disease status criteria outlined in the table below. Diagnoses must be confirmed by the National Cancer Institute (NCI) laboratory of pathology.
- Recipients with acute myeloid leukemia (AML) in first complete remission (CR1) must have one of the following:
- Adverse cytogenetics (as evaluated by history) as defined as complex karyotype (\> 3 abnormalities); inv(3) or t(3;3); t(6;9); t(6;11); monosomy 7; trisomy 8, alone or with an abnormality other than t(8;21), t(9;11), inv(16) or t(16;16); or t(11;19)(q23;p13.1) or adverse-risk per European LeukemiaNet (ELN) 2017 criteria.
- Intermediate-risk disease, such as cytogenetically normal AML (CN-AML) with mutations in FMS-like tyrosine kinase 3 (FLT3), DNA methyl transferase 3A (DMNT3A), or additional sex coombs like 1 (ASXL1) or per ELN 2017 criteria.
- Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy.
- Secondary AML, defined as AML related to antecedent myeloid neoplasm or cytotoxic chemotherapy.
- Hyperleukocytosis, white blood cell (WBC) \> 100,000, at diagnosis.
- +33 more criteria
You may not qualify if:
- Active infection that is not responding to antimicrobial therapy.
- Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid (CSF) cytology or parenchymal lesions visible by computed tomography (CT) or magnetic resonance imaging (MRI).
- Previous other malignancies unless they have undergone curative intent therapy for that malignancy and (1) have had no evidence of that disease for 5 years, and/or (2) be deemed at low risk for recurrence (less than or equal to 20% at 5 years).
- Human immunodeficiency virus (HIV) positive patients are ineligible as allogeneic stem cell transplant is not yet a proven approach in this patient population, and patients are at increased risk of lethal infections when treated with marrow suppressive therapy.
- Pregnant women are excluded from this study because palifermin has been shown to be embryotoxic and fetotoxic in animal studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with palifermin, breastfeeding should be discontinued for the duration of active study therapy. These potential risks may also apply to other agents used in this study.
- History of psychiatric disorder or any other condition which may compromise compliance with transplant protocol or expose patient to unnecessary risk as determined by principal investigator or lead associate investigator.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
National Marrow Donor Program
Minneapolis, Minnesota, 55401, United States
Related Publications (1)
Schulz E, Curtis LM, Holtzman NG, Steinberg SM, Wloka K, Ostojic A, Mina A, El Jurdi N, Pirsl F, Carpenter A, Golagha M, Sirajuddin A, Heller T, Shaffer BC, Hakim FT, Rubin JS, Gress RE, Pavletic SZ. Phase 1/2 study of high-dose palifermin for GVHD prophylaxis in patients undergoing HLA-matched unrelated donor HCT. Blood. 2025 Aug 21;146(8):944-950. doi: 10.1182/blood.2024028303.
PMID: 40331908DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Najla El Jurdi
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Alain Mina, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 4, 2015
First Posted
February 5, 2015
Study Start
September 24, 2015
Primary Completion
December 1, 2024
Study Completion
March 25, 2025
Last Updated
September 30, 2025
Results First Posted
June 5, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.