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

NCT00189488 | Completed Phase 2 Results

• 1 other identifier: 20040213
• Study Type: interventional
• Target: 155
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Graft Versus Host Disease; Hematologic Malignancies

Keywords

Hematological Malignancies; Graft-versus-host-disease; Oral Mucositis; Allogeneic Transplantation

Outcome Measures

Primary Outcomes (1)

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

  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.

  From transplant (Day 0) until Day 100

Secondary Outcomes (7)

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

  From transplant (Day 0) until Day 100

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

  Day 11

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

  From transplant (Day 0) until Day 100

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

  From transplant (Day 0) until Day 100

• Number of Participants With Parenteral or Transdermal Opioid Analgesic Use

  From transplant (Day 0) until Day 100

Study Arms (2)

Palifermin

EXPERIMENTAL

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.

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

Placebo

PLACEBO COMPARATOR

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.

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

Interventions

Palifermin DRUG

Administered as an intravenous (IV) bolus.

Also known as: Recombinant human keratinocyte growth factor (rHuKGF), Kepivance

Palifermin

Placebo DRUG

Administered as an intravenous (IV) bolus.

Placebo

Conditioning Regimen OTHER

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 \[Mel dose \> 140 mg/m\^2\])

Palifermin; Placebo

Allogeneic stem cell transplant PROCEDURE

Allogeneic marrow/peripheral blood progenitor cell transplantation

Palifermin; Placebo

Methotrexate DRUG

Palifermin; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%
• years of age or older at time of informed consent
• Before any study-specific procedure, the appropriate written informed consent must be obtained

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Amgen: collaborator

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms; Stomatitis

Interventions

Fibroblast Growth Factor 7; Transplantation Conditioning; Methotrexate

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Hans Olivecrona, MD PhD
• Organization: Biovitrum

hans.olivecrona@sobi.com

+46 8 697 20 00

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 19, 2005
• Study Start: December 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: August 1, 2013
• Last Updated: September 15, 2014
• Results First Posted: September 15, 2014

Record last verified: 2014-09