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

Sobi

Status and phase: Completed; Phase 2

Conditions: Graft Versus Host Disease; Hematologic Malignancies

Treatments: Drug: Placebo; Drug: Methotrexate; Procedure: Allogeneic stem cell transplant; Other: Conditioning Regimen; Drug: Palifermin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00189488

20040213

Details and patient eligibility

About

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.

Enrollment: 155 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects with hematologic malignancies (including myelodysplastic syndromes [MDS]) who are considered eligible for Cyclophosphamide (Cy)/Total Body Irradiation(TBI) +/- Etoposide (VP-16); Total Body Irradiation(TBI)/ Etoposide(VP-16); Melphalan(Mel) / Total Body Irradiation(TBI); Busulfan(Bu)/ Cyclophosphamide(Cy); Busulfan(Bu)/ Melphalan (Mel); or Fludarabine(Flu)/ Melphalan(Mel) conditioning therapy with allogeneic stem cell support
• Subjects with a 6/6 Human Leukocyte Antigen (HLA)-matched family member or unrelated donor who would provide donor marrow/ peripheral progenitor stem cells. [For unrelated matched donors, molecular typing of class I and class II is mandatory]
• Karnofsky Performance Status >= 70%
• 18 years of age or older at time of informed consent
• Before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion criteria

• Cancer other than Non-Hodgkin's lymphoma, Hodgkin's disease, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome or multiple myeloma (except: adequately treated basal cell carcinoma of the skin)
• Prior autologous or allogeneic bone marrow or peripheral blood stem cell transplantation
• Previous use of palifermin
• Current active infection (including human immunodeficiency virus (HIV) and hepatitis) or oral mucositis
• Congestive heart failure as defined by New York Heart Association class III or IV
• Graft T-cell depletion for Graft-versus-host disease (GVHD) prophylaxis
• Inadequate renal function (serum creatinine > 1.5x the upper limit of normal per the institutional guidelines or clearance < 40 ml/min adjusted for age)
• Inadequate liver function (total bilirubin > 1.5x the upper limit of normal, aspartate aminotransferase (AST) > 3x upper limit of normal and/or alanine aminotransferase (ALT) > 3x upper limit of normal per the institutional guidelines)
• Inadequate pulmonary function as measured by a corrected DLCO (diffusing capacity of the lung for carbon monoxide lung function test) <50% of predicted
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)
• Subject of child-bearing potential is evidently pregnant (e.g. positive human chorionic gonadotropin- HCG test) or is breast feeding during Part A of the study
• Subject or partner of subject is not using or refuses to use adequate contraceptive precautions during Part A of the study
• Subject has known sensitivity to any of the products to be administered during dosing including Escherichia coli-derived products
• Subject was previously randomized into this study
• Subject will not be available for follow-up assessments
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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155 participants in 2 patient groups, including a placebo group

Palifermin

Experimental group

Description:

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.

Treatment:

Drug: Palifermin

Other: Conditioning Regimen

Drug: Methotrexate

Procedure: Allogeneic stem cell transplant

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Other: Conditioning Regimen

Drug: Methotrexate

Procedure: Allogeneic stem cell transplant