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

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.

Conditions

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

Interventions

BIOLOGICAL

Rituximab

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

DRUG

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.

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.

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.

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.

PROCEDURE

Hematopoietic stem cell transplant

Hematopoietic stem cell transplant

DRUG

Palifermin

Escalating doses of palifermin given during transplant phase.

DRUG

Acetaminophen

Before each infusion of rituximab as indicated.

DRUG

Diphenhydramine

Before each infusion of rituximab as indicated.

DRUG

Prednisone

For engraftment syndrome.

DRUG

Epinephrine

Emergency medication as indicated.

OTHER

IV Saline

Before each infusion of rituximab as indicated.

DIAGNOSTIC_TEST

ECG

As indicated.

DIAGNOSTIC_TEST

ECHO

As indicated.

DIAGNOSTIC_TEST

MUGA

As indicated.

DIAGNOSTIC_TEST

DEXA

As indicated.

DIAGNOSTIC_TEST

CT chest

As indicated.

DIAGNOSTIC_TEST

PET

As indicated.

DIAGNOSTIC_TEST

MRI

As indicated.

PROCEDURE

BM aspirate

As indicated.

PROCEDURE

BM biopsy

As indicated.

PROCEDURE

Lumbar puncture

As indicated.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Alain Mina, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-09-24

Primary Completion

2024-12-01

Completion

2025-03-25

FDA Drug

Yes

Countries

• United States

Study Locations