Graft Versus Host DiseasePhase 2NCT00189488
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 Phase 2 study testing Palifermin, Conditioning Regimen and Allogeneic stem cell transplant in people with Graft Versus Host Disease and Hematologic Malignancies, run by Swedish Orphan Biovitrum.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease, Hematologic Malignancies
- What is being tested?
- Palifermin, Conditioning Regimen and Allogeneic stem cell transplant
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 155 participants
- Where
- No sites listed yet
- Study dates
- Dec 2005to Aug 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
Official title: 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
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.
- Being tested
- Palifermin, Placebo, Conditioning Regimen, Allogeneic stem cell transplant, Methotrexate
- Keywords
- Hematological Malignancies, Graft-versus-host-disease, Oral Mucositis, Allogeneic Transplantation
- Medical subject headings
- Graft vs Host Disease, Hematologic Neoplasms, Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called Recombinant human keratinocyte growth factor (rHuKGF), Kepivance
Administered as an intravenous (IV) bolus.
PlaceboDrug
Administered as an intravenous (IV) bolus.
Conditioning RegimenOther
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])
Allogeneic stem cell transplantProcedure or surgery
Allogeneic marrow/peripheral blood progenitor cell transplantation
MethotrexateDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo; Other: Conditioning Regimen; Procedure: Allogeneic stem cell transplant; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From transplant (Day 0) until Day 100
Secondary outcomes (7)
Number of Participants With Grade 2 to 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 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.
Measured: From transplant (Day 0) until Day 100
Number of Participants With Day 11 Methotrexate Graft Versus Host Disease Prophylaxis Administration
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.
Measured: Day 11
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
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.
Measured: From transplant (Day 0) until Day 100
Duration of Severe Oral Mucositis (WHO Grade 3 and 4)
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.
Measured: From transplant (Day 0) until Day 100
Number of Participants With Parenteral or Transdermal Opioid Analgesic Use
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.
Measured: From transplant (Day 0) until Day 100
Duration of Hospitalization
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.
Measured: From transplant (Day 0) until Day 100
Area Under the Curve (AUC) of Mouth and Throat Soreness Score
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).
Measured: The first day of study drug administration through Day 28.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study startDec 2005
- Primary completionNov 2008
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00189488
- Sponsor's protocol ID
- 20040213
- Status last verified
- Sep 2014
- First submitted
- 15 Sep 2005
- Last updated
- 15 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00189488
- Acronym / sponsor ID
- 20040213
- Keywords
- Hematological Malignancies, Graft-versus-host-disease, Oral Mucositis, Allogeneic Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- Dec 2005
- Primary completion
- Nov 2008 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 19 Sep 2005 (estimated)
- Results
- Posted 15 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Palifermin | Experimental | Drug: Palifermin, Other: Conditioning Regimen, Procedure: Allogeneic stem cell transplant, Drug: MethotrexatePalifermin 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 | Placebo comparator | Drug: Placebo, Other: Conditioning Regimen, Procedure: Allogeneic stem cell transplant, Drug: MethotrexatePlacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaliferminAlso: Recombinant human keratinocyte growth factor (rHuKGF), KepivanceAdministered as an intravenous (IV) bolus. | Drug | Palifermin |
| PlaceboAdministered as an intravenous (IV) bolus. | Drug | Placebo |
| Conditioning RegimenEach 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]) | Other | Palifermin, Placebo |
| Allogeneic stem cell transplantAllogeneic marrow/peripheral blood progenitor cell transplantation | Procedure or surgery | Palifermin, Placebo |
| Methotrexate | Drug | Palifermin, Placebo |
Primary outcome
Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD)
Time frame: From transplant (Day 0) until Day 100
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.
7 secondary outcomes
Number of Participants With Grade 2 to 4 Acute Graft Versus Host Disease (GVHD)
Time frame: From transplant (Day 0) until Day 100
Number of Participants With Day 11 Methotrexate Graft Versus Host Disease Prophylaxis Administration
Time frame: Day 11
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Time frame: From transplant (Day 0) until Day 100
Duration of Severe Oral Mucositis (WHO Grade 3 and 4)
Time frame: From transplant (Day 0) until Day 100
Number of Participants With Parenteral or Transdermal Opioid Analgesic Use
Time frame: From transplant (Day 0) until Day 100
Duration of Hospitalization
Time frame: From transplant (Day 0) until Day 100
Area Under the Curve (AUC) of Mouth and Throat Soreness Score
Time frame: The first day of study drug administration through Day 28.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Palifermin, Conditioning Regimen and Allogeneic stem cell transplant in people with Graft Versus Host Disease and Hematologic Malignancies, run by Swedish Orphan Biovitrum.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD) (time frame: From transplant (Day 0) until Day 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2014.