Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

NCT ID: NCT02356159

Last Updated: 2025-09-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-24

Study Completion Date

2025-03-25

Brief Summary

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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.

Detailed Description

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Background:

* Graft versus host disease (GVHD) and impaired immune reconstitution are major transplant complications and barriers to improving outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) for hematologic malignancies. GVHD is initiated when donor T-cells become alloreactive against recipient major or minor histocompatibility antigens. This process may be exacerbated during the transplantation process by exposure of tissue antigens to donor T-lymphocytes after chemotherapy-induced injury.
* Palifermin, a recombinant keratinocyte growth factor-1 (KGF-1), imitates the actions of intrinsic KGF and binds to the Fibroblast growth factor (FGF) receptor 2b, which is expressed in the epidermis, oral mucosa, gastrointestinal (GI) mucosa and urothelium, thereby increasing the regenerative capacity of these tissues. Palifermin has been shown to reduce the duration and severity of oral mucositis after intensive chemo-radiotherapy and autologous HSCT for hematologic cancers and is Food and Drug Administration (FDA) approved. In pre-clinical studies, palifermin has been shown to have an effect on control of acute or chronic GVHD and immune reconstitution after alloHSCT. However, subsequent clinical studies in alloHSCT indicate that the dose and schedule of palifermin as currently

used in humans does not optimize its activity in terms of prevention of GVHD or thymus recovery following alloHSCT.

\- We hypothesize that higher doses of palifermin in the immediate pre alloHSCT conditioning setting will lead to enhanced thymopoiesis, decreased chronic GVHD, and improved immune reconstitution. A dose escalation study is necessary to determine safe dosing levels in persons undergoing alloHSCT.

Objectives:

* The primary objective of the phase I portion is to assess the safety and tolerability of the administration of the recombinant keratinocyte growth factor (KGF) palifermin in alloHSCT using unrelated donor peripheral blood stem cells.
* The primary objective of the phase II portion is to determine the incidence of severe chronic GVHD after the addition of palifermin to TMS (tacrolimus, methotrexate and sirolimus) based GVHD prophylaxis delivered in the identical fashion to the NCI 07-C-0195 study.

Eligibility:

* Adults (greater than or equal to 18 years) with advanced or high-risk hematologic malignancies (including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), chronic myeloid leukemia (CML), multiple myeloma, and myeloproliferative neoplasm (MPN) who lack a suitable human leukocyte antigens (HLA)-matched sibling donor.
* An unrelated donor matched at a minimum of 8 alleles (HLA-A,-B,-C, and major histocompatibility complex, class II, DR beta 1 (DRB1) by high-resolution typing, identified through the National Marrow Donor Program.
* Karnofsky greater than or equal to 60 and acceptable organ functions.

Design:

* Patients will receive disease-specific induction chemotherapy etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride with fludarabine and rituximab (EPOCH-F/R or fludararbine, ara-c, granulocyte colony-stimulating factor (FLAG) prior to transplant as needed for disease control and immune depletion.
* All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m\^2/day intravenous (IV) for 4 days and fludarabine 30 mg/m\^2/day for 4 days (transplant days -6 to -3).
* All patients will receive a peripheral blood stem cell product from an unrelated donor matched at HLA-A, -B, -C, -DRB1 (8/8) by high-resolution typing.
* Palifermin will be administered in a phase 1, open label design with the following proposed schedule:

* Dose level 1: 180 mcg/kg on day -7
* Dose level 2: 360 mcg/kg on day -7
* Dose level 3: 540 mcg/kg on day -7
* Dose level 4: 720 mcg/kg on day -7
* The phase I portion will be conducted in a standard 3+3 design; the maximum possible number of patients accrued to this portion will be 24.
* The maximum tolerated dose (MTD) from the phase I portion of the study will be used to conduct a phase II study. Total accrual on the phase II study will be 27 patients, including 3-6 patients treated at the MTD in the phase I portion of the study

Conditions

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Myelodysplastic Syndromes Hodgkin's Lymphoma Non-Hodgkin's Lymphoma Acute Leukemia Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1/Phase 1: Dose Escalation Arm - Palifermin

Induction chemotherapy, then palifermin at escalating doses, then conditioning chemotherapy, then allogeneic stem cell transplant, then immunosuppression.

Group Type EXPERIMENTAL

Rituximab

Intervention Type BIOLOGICAL

Rituximab: 375 mg/m\^2 intravenous (IV) day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.

Conditioning chemotherapy

Intervention Type DRUG

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.

TMS

Intervention Type DRUG

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.

FLAG

Intervention Type DRUG

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.

EPOCH-F

Intervention Type DRUG

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

Intervention Type PROCEDURE

Hematopoietic stem cell transplant

Palifermin

Intervention Type DRUG

Escalating doses of palifermin given during transplant phase.

Acetaminophen

Intervention Type DRUG

Before each infusion of rituximab as indicated.

Diphenhydramine

Intervention Type DRUG

Before each infusion of rituximab as indicated.

Prednisone

Intervention Type DRUG

For engraftment syndrome.

Epinephrine

Intervention Type DRUG

Emergency medication as indicated.

IV Saline

Intervention Type OTHER

Before each infusion of rituximab as indicated.

ECG

Intervention Type DIAGNOSTIC_TEST

As indicated.

ECHO

Intervention Type DIAGNOSTIC_TEST

As indicated.

MUGA

Intervention Type DIAGNOSTIC_TEST

As indicated.

DEXA

Intervention Type DIAGNOSTIC_TEST

As indicated.

CT chest

Intervention Type DIAGNOSTIC_TEST

As indicated.

PET

Intervention Type DIAGNOSTIC_TEST

As indicated.

MRI

Intervention Type DIAGNOSTIC_TEST

As indicated.

BM aspirate

Intervention Type PROCEDURE

As indicated.

BM biopsy

Intervention Type PROCEDURE

As indicated.

Lumbar puncture

Intervention Type PROCEDURE

As indicated.

2/Phase II Arm - Palifermin at the Recommended Phase 2 Dose

Induction chemotherapy, then palifermin at the recommended phase 2 dose determined in Phase 1, then conditioning chemotherapy, then allogeneic stem cell transplant, then immunosuppression.

Group Type EXPERIMENTAL

Rituximab

Intervention Type BIOLOGICAL

Rituximab: 375 mg/m\^2 intravenous (IV) day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.

Conditioning chemotherapy

Intervention Type DRUG

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.

TMS

Intervention Type DRUG

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.

FLAG

Intervention Type DRUG

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.

EPOCH-F

Intervention Type DRUG

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

Intervention Type PROCEDURE

Hematopoietic stem cell transplant

Palifermin

Intervention Type DRUG

Escalating doses of palifermin given during transplant phase.

Acetaminophen

Intervention Type DRUG

Before each infusion of rituximab as indicated.

Diphenhydramine

Intervention Type DRUG

Before each infusion of rituximab as indicated.

Prednisone

Intervention Type DRUG

For engraftment syndrome.

Epinephrine

Intervention Type DRUG

Emergency medication as indicated.

IV Saline

Intervention Type OTHER

Before each infusion of rituximab as indicated.

ECG

Intervention Type DIAGNOSTIC_TEST

As indicated.

ECHO

Intervention Type DIAGNOSTIC_TEST

As indicated.

MUGA

Intervention Type DIAGNOSTIC_TEST

As indicated.

DEXA

Intervention Type DIAGNOSTIC_TEST

As indicated.

CT chest

Intervention Type DIAGNOSTIC_TEST

As indicated.

PET

Intervention Type DIAGNOSTIC_TEST

As indicated.

MRI

Intervention Type DIAGNOSTIC_TEST

As indicated.

BM aspirate

Intervention Type PROCEDURE

As indicated.

BM biopsy

Intervention Type PROCEDURE

As indicated.

Lumbar puncture

Intervention Type PROCEDURE

As indicated.

Interventions

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Rituximab

Rituximab: 375 mg/m\^2 intravenous (IV) day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.

Intervention Type BIOLOGICAL

Conditioning chemotherapy

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.

Intervention Type DRUG

TMS

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.

Intervention Type DRUG

FLAG

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.

Intervention Type DRUG

EPOCH-F

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.

Intervention Type DRUG

Hematopoietic stem cell transplant

Hematopoietic stem cell transplant

Intervention Type PROCEDURE

Palifermin

Escalating doses of palifermin given during transplant phase.

Intervention Type DRUG

Acetaminophen

Before each infusion of rituximab as indicated.

Intervention Type DRUG

Diphenhydramine

Before each infusion of rituximab as indicated.

Intervention Type DRUG

Prednisone

For engraftment syndrome.

Intervention Type DRUG

Epinephrine

Emergency medication as indicated.

Intervention Type DRUG

IV Saline

Before each infusion of rituximab as indicated.

Intervention Type OTHER

ECG

As indicated.

Intervention Type DIAGNOSTIC_TEST

ECHO

As indicated.

Intervention Type DIAGNOSTIC_TEST

MUGA

As indicated.

Intervention Type DIAGNOSTIC_TEST

DEXA

As indicated.

Intervention Type DIAGNOSTIC_TEST

CT chest

As indicated.

Intervention Type DIAGNOSTIC_TEST

PET

As indicated.

Intervention Type DIAGNOSTIC_TEST

MRI

As indicated.

Intervention Type DIAGNOSTIC_TEST

BM aspirate

As indicated.

Intervention Type PROCEDURE

BM biopsy

As indicated.

Intervention Type PROCEDURE

Lumbar puncture

As indicated.

Intervention Type PROCEDURE

Other Intervention Names

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Rituxan Riabni Ruxience Truxima Fludarabine Cyclophosphamide Mesna Furosemide Tacrolimus Fludarabine Cytarabine Filgrastim Etoposide phosphate Prednisone Vincristine sulfate Cyclophosphamide Doxorubicin hydrochloride Fludarabine HSCT Kepivance Tylenol Ofirmev FeverAll Benadryl Banophen Nytol Rayos Deltasone Prednisone Intensol Adrenaline Intravenous saline Electrocardiogram Echocardiogram Multigated acquisition Dual-energy X-ray absorptiometry Computed tomography chest Positron-emission tomography Magnetic resonance imaging Bome marrow aspirate Bone marrow biopsy LP

Eligibility Criteria

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Inclusion Criteria

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.
* Recipients with ALL in CR1 must have one of the following:
* Adverse cytogenetics defined as translocations involving t(4;11), t(1;19), t(8;14), 11q23, t(9;22) or bcr-abl rearrangement, Philadelphia chromosomelike (Ph-like ALL), or complex cytogenetic abnormalities.
* Presence of minimal residual disease using multicolor flow cytometry or other analytic technique after primary induction chemotherapy.
* Primary induction failure, defined as failure to achieve complete remission (CR) with primary induction chemotherapy.
* Recipients with myelofibrosis must have at least 2 of the following features, or be Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high risk:
* Hemoglobin \< 10 g/dl, or \> 10 g/dl with transfusion dependence.
* WBC \< 4,000 or \> 30,000/mm\^3 or requires cytoreductive therapy to maintain WBC \< 30,000/mm\^3.
* Abnormal cytogenetics.
* Patients with lymphoma must ideally have at least stable disease from last therapy however if the PI or LAI believes there is a high likelihood of response to induction chemotherapy (EPOCH-F+/R), then the patient may be enrolled on the induction phase arm. For enrollment on the research phase arm, the patient must have at lease stable disease which is defined as:
* Absence of disease progression for at least 8 weeks after previous therapy or 12 weeks after autologous transplantation.
* Patients who are less than 8 weeks from previous therapy or 12 weeks from autologous transplantation may participate in the study at the discretion of the PI or LAI as long as they do not have progressive disease.
* Multiple myeloma in complete remission is defined as per Dr. Brian G.M. Durie (Durie BG) et al.
* Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in the bone marrow. CR requires two consecutive assessments by serum and urine immunofixation made at any time prior to enrollment. CR also requires no known evidence of progressive or new bone lesions if radiographic studies are performed. Confirmation with repeat bone marrow is not needed.
* The recipient has acceptable end organ function as defined by:
* Diffusing capacity for carbon monoxide (DLCO) \> 50% of the expected value (using United States of America (USA)-Information Technology Service (ITS)-National Institutes of Health (NIH) equation) when corrected for Hgb (DLCO Adj.)
* 24hr creatinine clearance or calculated (using the Cockcroft-Gault formula) creatinine clearance \> 60 ml/min/1.73 (induction phase only)
* Left ventricular ejection fraction \> 45%
* Serum total bilirubin less than 2.5 mg/dl, and serum alanine aminotransferase (ALT) and aspartate transferase (AST) values less than or equal to 2.5 times the upper limit of normal. Patients with elevations of serum total bilirubin up to 10 mg/dl and/or ALT or AST up to 10 times the upper limit of normal may be considered for participation if such elevations are thought to be due to liver involvement by malignancy. However, in these latter patients, if the bilirubin (BR) level does not decrease to less than or equal to 2.5 mg/dl, or AST/ALT do not decrease to less than or equal to 2.5 times the upper limit of normal after induction chemotherapy, eligibility for the transplant (research) phase will be at the discretion of the principal investigator (PI).
* Patients who are hepatitis B core antibody positive and or have positive hepatitis B surface antigen will require hepatology consultation. The risk/benefit profile of transplant and hepatitis B will be discussed with the patient and eligibility determined by the PI or the LAI.
* Patient may have a hepatitis C infection. However, each patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis C will be discussed with the patient and eligibility determined by the PI or the LAI.
* Palifermin has had embryotoxic and fetotoxic effects in animal studies. For this reason and because the other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of active study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.


Verification of donor eligibility (clearance must be received from the NMDP)

* Donors are evaluated by NMDP affiliated donor centers per NMDP Standards.

* Donors who are medically suitable, but ineligible by Food and Drug Administration (FDA) guidelines may still donate peripheral blood stem cells (PBSC) with documentation of urgent medical need by the PI.
* Patients who receive stem cell products from ineligible donors will be informed of any increase in risk of transfusion-related diseases prior to initiation of conditioning chemotherapy.
* Donors who are ineligible or unwilling to donate bone marrow will not be eligible to donate to study recipients. However, in the event that the patient has already begun conditioning chemotherapy and a donor PBSC collection is terminated early for donor-related medical concerns, a bone marrow graft may be infused. Should this occur, the recipient will continue to be managed on this protocol for all transplant-related care and complications. Patient will stay on study, but clinical outcomes will not be eligible for the statistics and end point calculations.
* Inadequate stem cell collection from the selected donor is defined as less than or equal to 2 x 10\^6 cluster of differentiation 34 (CD34+) cells/kg. In most cases, donor cell collections are infused fresh. If a fresh collection is found to have an inadequate cell count, the cells will still be infused, but the recipient will be removed from the study and managed clinically for all transplant related care and complications on this protocol. If the patient fails to engraft, the donor may be requested for a second collection or an emergency bone marrow harvest at the discretion of the PI and NMDP Medical Director. In the event of an inadequate collection obtained prior to patient conditioning, the donor may be asked to donate a second time, or another eligible donor may be requested.
* Renal and hepatic function continues to meet eligibility criteria, reassessed as follows:

* 24-hour creatinine clearance or calculated (using the Cockcroft-Gault formula) creatinine clearance \> 60 mL/min/1.73 m\^2 (induction phase only)
* (((140-age)\*mass(kg))/(72\*serum creatinine (mg/dL))) x 1.73 m\^2/patients body surface area (BSA)
* If the patient is female, multiply the above by 0.85
* In patients with suspected liver disease, bilirubin must be less than or equal to 2.5 mg/dL, AST and ALT must be less than or equal to 2.5 times institutional upper limit of normal (ULN)
* The malignancy must be restaged prior to research phase and must not have progressed during induction chemotherapy (stable disease or better). Persons with acute leukemia, myelodysplastic syndrome (MDS)/refractory anemia with excess blasts (RAEB)-I or II or chronic myeloid leukemia (CML) with previous accelerated or blast phase must have \<5% blasts in the bone marrow. Persons with chronic phase CML may have up to 10% blasts in the bone marrow.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Najla El Jurdi

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alain Mina, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

National Marrow Donor Program

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 40331908 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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Other Identifiers

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15-C-0067

Identifier Type: -

Identifier Source: secondary_id

150067

Identifier Type: -

Identifier Source: org_study_id

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