Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Mouth and Tooth Diseases

Digestive System Diseases

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Stomatitis

Mucositis

Hematologic Diseases

Homologous Wasting Disease

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Etoposide

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Methotrexate

Melphalan

Etoposide phosphate

Busulfan

Mitogens

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m\^2 respectively.

Placebo to palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to palifermin 180 μg/kg once prior to transplant and at least 96 hours from previous placebo to palifermin 60 μg/kg dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m\^2 respectively.

Administered as an intravenous (IV) bolus.

Palifermin

Placebo

Each participant received 1 of the following conditioning regimens:

* Cyclophosphamide (Cy) / total body irradiation (TBI) with and without etoposide (VP-16)
* TBI/VP-16
* Melphalan (Mel)/TBI (TBI regimens must include fully ablative doses ie \> 1100 cGy; sequence of chemotherapy/radiation (CT/RT) flexible)
* Busulfan (Bu)/Cy
* Bu/Mel (non-TBI but fully ablative regimens/doses \[Mel dose \> 140 mg/m\^2\])
* Fludarabine (Flu)/Mel (non-TBI but fully ablative regimens/doses \[Mel dose \> 140 mg/m\^2\])

Conditioning Regimen

Allogeneic marrow/peripheral blood progenitor cell transplantation

Allogeneic stem cell transplant

The main purpose of this study is to evaluate the effect of palifermin versus placebo in the reduction of severe acute graft versus host disease (GVHD) and severe oral mucositis.

Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation

A Randomized, Double-blind, Placebo-controlled Trial to Evaluate Palifermin (rHuKGF) in the Reduction of Acute Graft Versus Host Disease in Subjects With Hematologic Malignancies Undergoing Allogeneic Marrow/PBPC Transplantation

GVHD was graded using the modified Keystone Criteria weekly during the first 2 months after stem cell infusion, then every other week until Day 100.

Severity was determined clinically (based on physical exam and laboratory serum values) and from biopsies of affected organs whenever possible. The degree of GVHD in individual organs was scored by at least 2 assessors.

Grade 3 GVHD = total bilirubin 3.1 - 15.0 mg/dL or ≥ 1000 mL/day diarrhea or severe abdominal pain with/without ileus.

Grade 4 GVHD = skin involvement with bullous formation or total bilirubin \> 15.0 mg/dL.

GVHD was graded using the modified Keystone Criteria weekly during the first 2 months after stem cell infusion, then every other week until Day 100.

Severity was determined clinically (based on physical exam and laboratory serum values) and from biopsies of affected organs whenever possible. The degree of GVHD in individual organs was scored by at least 2 assessors.

Grade 2 GVHD = \> 50% skin involvement or total bilirubin 2.0 - 3.0 mg/dL or 500 - 999 mL/day diarrhea, or persistent nausea with histologic evidence.

Grade 3 GVHD = total bilirubin 3.1 - 15.0 mg/dL or ≥ 1000 mL/day diarrhea or severe abdominal pain with/without ileus.

Grade 4 GVHD = skin involvement with bullous formation or total bilirubin \> 15.0 mg/dL.

Low dose methotrexate is widely used in regimens to prophylax against acute GVHD. Methotrexate was administered on days 1, 3, 6 and 11 (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m\^2, respectively.

Oral cavity assessments were performed by a trained assessor using the World Health Organization (WHO) oral toxicity scale. Daily oral mucositis assessments were performed:

* while participants were hospitalized, including the day of discharge (maximum until day 28);
* after discharge until the oral mucositis grade returns to a WHO grade ≤ 2.

The WHO oral toxicity criteria are: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.

The duration of severe oral mucositis was calculated as the number of days from the onset of severe mucositis (first time a WHO grade of 3 or 4 was observed) to the last day when severe mucositis was observed. If oral mucositis assessments were recorded as missed visits immediately prior to or immediately after severe mucositis was recorded, the missed visits were considered to be severe oral mucositis.

Includes nonprophylactic intravenous opioid analgesics (fentanyl, morphine, morphine sulphate, hydromorphone, meperidine) and transdermal opioid analgesics (fentanyl patch) for the indication of oral mucositis and dysphagia.

Duration of hospitalization was defined as the number of days a participant stayed in hospital (hospitalized) during the period starting from the day of the transplant (Day 0) to the 100th day following the transplant.

The modified Oral Mucositis Daily Questionnaire (OMDQ) is a self-reported tool that evaluates overall health, mouth and throat soreness (MTS) and activity limitations due to MTS.

The modified OMDQ was completed once daily beginning with the first day of study drug administration through day 28.

The area under the curve of mouth and throat soreness score was assessed from the question "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness).

Amgen

Swedish Orphan Biovitrum

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Two participants were randomized to the Placebo arm but received palifermin inadvertently and were summarized in Palifermin arm.

Placebo to 60 μg/kg palifermin administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to 180 μg/kg palifermin administered once, prior to transplant and at least 96 hours from the previous placebo dose.

Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg.

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Native Hawaiian or Other Pacific Islander

Other

Race/Ethnicity, Customized

Leukemia - all types

Acute lymphoblastic leukemia

Acute myelogenous leukemia

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

Hodgkin's disease

Non-Hodgkin's lymphoma

Multiple Myeloma

Myelodysplastic Syndrome

Acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia are subsets of leukemia.

Type of diagnosis

Related Family Member

Unrelated

Donor type

Marrow

Peripheral blood progenitor cell(s)

Donor source

Prior radiotherapy

Hans Olivecrona, MD PhD

Primary Analysis Set (consisting of all randomized participants) with GVHD assessments.

Number of Participants With Grade 2 to 4 Acute Graft Versus Host Disease (GVHD)

Primary Analysis Set (consisting of all randomized participants) with GVHD assessments. Efficacy analyses were according to randomized treatment assignment.

Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD)

Number of Participants With Day 11 Methotrexate Graft Versus Host Disease Prophylaxis Administration

Participants with "Unknown" incidence are treated as "Yes" when constructing the differences, 95% confidence intervals and p-value.

Unknown

Number of Participants With Severe (Grade 3 or 4) Oral Mucositis

Duration of Severe Oral Mucositis (WHO Grade 3 and 4)

Number of Participants With Parenteral or Transdermal Opioid Analgesic Use

PaPalifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg.

Duration of Hospitalization

Area Under the Curve (AUC) of Mouth and Throat Soreness Score

Placebo to 60 μg/kg palifermin administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to 180 μg/kg palifermin once prior to transplant and at least 96 hours from the previous placebo dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m\^2 respectively.

Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m\^2 respectively

Spots Global Cancer Trial Database for Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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