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 donor s 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.
To see if high doses of palifermin before chemotherapy are safe, prevent chronic GVHD, and
improve immune function after transplant.
Adults 18 years of age or older with blood or bone marrow cancer with no HLA-matched
sibling, but with a possible HLA-matched donor.
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
Get a central line catheter if they do not have one.
Have 1-3 rounds of chemotherapy.
Take more tests to make sure they can have the transplant, including medical history,
physical exam, and CT scan.
Get palifermin by IV and more chemotherapy. They will get other drugs, some they will
take for 6 months.
Participants will get the SCT.
After transplant, participants will:
Be hospitalized at least 3-4 weeks.
Have tests for GVHD at 60 days and 6 months. These include mouth and skin photos and
Stay near D.C. for 3 months.
Visit NIH 5 times the first 2 years, then yearly. They may have scans and biopsies.
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 FGF receptor 2b, which is expressed in the epidermis,
oral mucosa, 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 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.
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
Adults (greater than or equal to 18 years) with advanced or high risk hematologic
malignancies (including AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPN)who
lack a suitable HLA-matched sibling donor.
An unrelated donor matched at a minimum of 8 alleles (HLA-A,-B,-C, and DRB1) by
high-resolution typing, identified through the National Marrow Donor Program.
Karnofsky greater than or equal to 60 and acceptable organ functions.
Patients will receive disease-specific induction chemotherapy (EPOCH-F/R or 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 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
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
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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