Gastrointestinal MucositisPhase 2NCT00728585
Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant
A Phase 2 study testing Palifermin in people with Gastrointestinal Mucositis and Malignant Neoplasm, run by Children's Oncology Group.
Trial summary
This randomized phase II trial is studying palifermin to see how well it works compared with a placebo in preventing oral mucositis caused by chemotherapy and/or radiation therapy in young patients undergoing stem cell transplant. Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Gastrointestinal Mucositis, Malignant Neoplasm
- What is being tested?
- Palifermin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 13 Mar 2008to 8 May 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 1 year to 16 years
- All sexes
- No healthy volunteers
- Child
Criteria:
- Patients undergoing myeloablative autologous or allogeneic hematopoietic stem cell transplantation (HSCT) for any indication
- Any type of myeloablative HSCT conditioning regimen allowed
- Patients undergoing allogeneic HSCT may undergo 1 of the following types of donor stem cells:
- HLA-matched sibling or parent
- Partially matched family donor (mismatched for a single HLA locus [class I])
- Fully matched unrelated marrow or peripheral blood stem cell donor
- HLA-matched or partially mismatched (at least 4 of 6 match) cord blood (class I or II)
- Fertile patients must use effective contraception
- No HIV positivity
- No known sensitivity to any E. coli-derived products
- Known grade 1 to 2 allergic reactions to asparaginase allowed
- No prior grade 3-4 allergies to asparaginase or pegaspargase
- More than 30 days since prior and no concurrent treatment with any of the following therapies:
- Oral cryotherapy
- Glutamine as an oral supplement
- Traumeel
- Gelclair
- Oral vancomycin paste
- Low-level laser therapy
- An investigational product or device in another clinical trial
- No prior palifermin or other keratinocyte growth factors
- No other concurrent cytotoxic drugs for conditioning or graft-vs-host disease prophylaxis (intrathecal methotrexate or cytarabine for CNS involvement allowed)
- Not pregnant or nursing
About this study
Official title: A Group-Wide Double-Blind Randomized Placebo-Controlled Trial of Palifermin to Prevent Chemotherapy and/or Radiotherapy Induced Oral Mucositis in Children Undergoing Autologous or Allogeneic Hematopoietic Stem Cell Transplantation
This randomized phase II trial is studying palifermin to see how well it works compared with a placebo in preventing oral mucositis caused by chemotherapy and/or radiation therapy in young patients undergoing stem cell transplant. Palifermin may help relieve or prevent oral mucositis caused by chemotherapy and radiation therapy in young patients undergoing stem cell transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare whether palifermin versus placebo administered to pediatric patients three days prior to conditioning and three days after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) is associated with a reduction in the incidence of WHO grade 3 or 4 oral mucositis.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of palifermin. II. To evaluate the long-term effects of palifermin on disease outcome and survival.
III. To compare the incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents), and incidence and duration of total parenteral nutrition (TPN) administration in patients treated with these regimens.
IV. To compare the incidence of febrile neutropenia and invasive bacterial infections in patients treated with these regimens.
TERTIARY OBJECTIVES:
- To determine whether palifermin versus placebo reduces the incidence of WHO grade 3 or 4 oral mucositis among allogeneic HSCT pediatric patients receiving methotrexate as graft-versus-host disease (GVHD) prophylaxis.
II. To determine whether palifermin versus placebo reduces acute and chronic GVHD after allogeneic HSCT.
III. To describe health care utilization (hospitalization duration, and administration of antibiotics, TPN, nasogastric-, nasojejunal- or gastrostomy-administered enteral nutrition, and blood products) in pediatric patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to age in years (1 to 2 vs 3 to 11 vs 12 to 16), type of hematopoietic stem cell transplantation (HSCT) (autologous vs allogeneic), conditioning regimen (either total-body irradiation [TBI] or melphalan vs neither TBI nor melphalan). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic HSCT.
ARM II: Patients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic HSCT.
Blood samples are collected at baseline, 32 days, and 100 days after HSCT to evaluate the immunogenicity of palifermin. Oral mucositis is assessed at baseline, daily for 8 days prior to and 32 days after HSCT, or until oral mucositis has resolved by the WHO Mucositis Scale, Oral Mucositis Assessment Scale (OMAS), modified Walsh mucositis scale, Oral Mucositis Daily Questionnaire (OMDQ), and the pain categorical rating scale.
After completion of HSCT, patients are followed periodically for up to 10 years.
- Conditions
- Gastrointestinal Mucositis, Malignant Neoplasm
- Being tested
- Palifermin, Placebo
- Medical subject headings
- Mucositis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor
Given IV
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (palifermin) | Experimental | Patients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation. Receives: Drug: Palifermin |
| Arm II (placebo) | Placebo comparator | Patients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of WHO grade 3 or 4 oral mucositis
The incidence of WHO grade 3 or 4 mucositis, the palifermin and placebo groups, will be compared using a generalized Cochran-Mantel-Haenszel method for general association as the primary analysis. In addition, this outcome will be examined using a logistic regression model; both approaches will account for the randomization strata. Potential confounders will be examined using multiple logistic regression models.
Measured: Up to day 32
Secondary outcomes (10)
Incidence of adverse events and laboratory abnormalities of palifermin according to using Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
Incidence of adverse events and laboratory abnormalities in the palifermin and placebo groups will be summarized for all study participants who receive at least one dose of study medication and also separately for autologous and allogeneic HSCT recipients using descriptive statistics. Time to neutrophil engraftment (first day of ANC 500/mm^3 for at least 2 consecutive days) will be examined in the palifermin and placebo groups and compared using the stratified log rank test. The incidence of serum anti-palifermin antibody formation will be summarized using descriptive statistics.
Measured: Up to 100 days post-HSCT
Long-term effects of palifermin on disease outcome and survival
Long-term outcomes (progression free survival, overall survival and second malignancies) will be examined using Kaplan-Meier and cumulative incidence curves and the compared using the stratified log rank test. These outcomes will be summarized among all study participants and also separately for autologous and allogeneic HSCT recipient.
Measured: Up to 10 years
Duration of WHO grade 3 or 4 oral mucositis
Duration of grade 3 or 4 oral mucositis, duration of total parenteral nutrition (TPN) administration and total dose of parenteral opioid analgesic will be compared between groups using a stratified Wilcoxon test. Severity of mucositis according to the Oral Mucositis Assessment Scale (OMAS), modified Walsh mucositis scale, pain categorical rating scale and Oral Mucositis Daily Questionnaire (OMDQ) scales will be compared between groups using the area under the curve (AUC).
Measured: Up to day 32
Daily OMAS scores
The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
Measured: Up to day 32
Daily modified Walsh mucositis scores
The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
Measured: Up to day 32
Daily pain categorical rating scales
The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
Measured: Up to day 32
Daily OMDQ
The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
Measured: Up to day 32
Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents)
Incidence of parenteral opioid analgesic use TPN administration will be compared between groups using a generalized Cochran- Mantel-Haenszel test.
Measured: Up to day 32
Incidence and duration of total parenteral nutrition administration
Incidence of parenteral opioid analgesic use TPN administration will be compared between groups using a generalized Cochran- Mantel-Haenszel test. If subjects are still receiving parenteral opioid analgesia or TPN on day 32, the subsequent stop date also will be collected.
Measured: Up to day 32
Incidence of febrile neutropenia and invasive bacterial infections
The incidence of febrile neutropenia and invasive bacterial infections will be compared using a generalized Cochran-Mantel-Haenszel test.
Measured: Up to day 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2008 (estimated)
- Study start13 Mar 2008
- Primary completion8 May 2009
Why it stopped: Withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal MucositisStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lillian Sung, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00728585
- Sponsor's protocol ID
- ACCL0521
- Other IDs
- NCI-2009-00329, CDR0000588622, ACCL0521, ACCL0521, U10CA095861
- Status last verified
- Apr 2013
- First submitted
- 5 Aug 2008
- Last updated
- 7 Aug 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Group-Wide Double-Blind Randomized Placebo-Controlled Trial of Palifermin to Prevent Chemotherapy and/or Radiotherapy Induced Oral Mucositis in Children Undergoing Autologous or Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00728585
- Acronym / sponsor ID
- ACCL0521
- Conditions
- Gastrointestinal Mucositis, Malignant Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Mar 2008 (actual)
- Primary completion
- 8 May 2009 (actual)
- First posted
- 6 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial is studying palifermin to see how well it works compared with a placebo in preventing oral mucositis caused by chemotherapy and/or radiation therapy in young patients undergoing stem cell transplant. Palifermin may help relieve or prevent oral mucositis caused by chemotherapy and radiation therapy in young patients undergoing stem cell transplant.
Detailed description
PRIMARY OBJECTIVES:
- To compare whether palifermin versus placebo administered to pediatric patients three days prior to conditioning and three days after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) is associated with a reduction in the incidence of WHO grade 3 or 4 oral mucositis.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of palifermin. II. To evaluate the long-term effects of palifermin on disease outcome and survival.
III. To compare the incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents), and incidence and duration of total parenteral nutrition (TPN) administration in patients treated with these regimens.
IV. To compare the incidence of febrile neutropenia and invasive bacterial infections in patients treated with these regimens.
TERTIARY OBJECTIVES:
- To determine whether palifermin versus placebo reduces the incidence of WHO grade 3 or 4 oral mucositis among allogeneic HSCT pediatric patients receiving methotrexate as graft-versus-host disease (GVHD) prophylaxis.
II. To determine whether palifermin versus placebo reduces acute and chronic GVHD after allogeneic HSCT.
III. To describe health care utilization (hospitalization duration, and administration of antibiotics, TPN, nasogastric-, nasojejunal- or gastrostomy-administered enteral nutrition, and blood products) in pediatric patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to age in years (1 to 2 vs 3 to 11 vs 12 to 16), type of hematopoietic stem cell transplantation (HSCT) (autologous vs allogeneic), conditioning regimen (either total-body irradiation [TBI] or melphalan vs neither TBI nor melphalan). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic HSCT.
ARM II: Patients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic HSCT.
Blood samples are collected at baseline, 32 days, and 100 days after HSCT to evaluate the immunogenicity of palifermin. Oral mucositis is assessed at baseline, daily for 8 days prior to and 32 days after HSCT, or until oral mucositis has resolved by the WHO Mucositis Scale, Oral Mucositis Assessment Scale (OMAS), modified Walsh mucositis scale, Oral Mucositis Daily Questionnaire (OMDQ), and the pain categorical rating scale.
After completion of HSCT, patients are followed periodically for up to 10 years.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (palifermin) | Experimental | Drug: PaliferminPatients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation. |
| Arm II (placebo) | Placebo comparator | Other: PlaceboPatients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation. |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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: Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth FactorGiven IV | Drug | Arm I (palifermin) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven IV | Other | Arm II (placebo) |
Primary outcome
Incidence of WHO grade 3 or 4 oral mucositis
Time frame: Up to day 32
The incidence of WHO grade 3 or 4 mucositis, the palifermin and placebo groups, will be compared using a generalized Cochran-Mantel-Haenszel method for general association as the primary analysis. In addition, this outcome will be examined using a logistic regression model; both approaches will account for the randomization strata. Potential confounders will be examined using multiple logistic regression models.
10 secondary outcomes
Incidence of adverse events and laboratory abnormalities of palifermin according to using Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
Time frame: Up to 100 days post-HSCT
Long-term effects of palifermin on disease outcome and survival
Time frame: Up to 10 years
Duration of WHO grade 3 or 4 oral mucositis
Time frame: Up to day 32
Daily OMAS scores
Time frame: Up to day 32
Daily modified Walsh mucositis scores
Time frame: Up to day 32
Daily pain categorical rating scales
Time frame: Up to day 32
Daily OMDQ
Time frame: Up to day 32
Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents)
Time frame: Up to day 32
Incidence and duration of total parenteral nutrition administration
Time frame: Up to day 32
Incidence of febrile neutropenia and invasive bacterial infections
Time frame: Up to day 32
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
Related trials for Gastrointestinal Mucositis
RecruitingPhase 2
Traditional Chinese Medicine Preparation Alleviates Radiotherapy-induced Oral Mucositis in Head and Neck Cancer Patients.
Radiotherapy-induced Oral Mucositis
RecruitingPhase 3
High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma, Stage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
RecruitingObservational study
Evaluation of 25(OH)D3 and LL-37 Levels in Periimplant Sulcus Fluid
Peri Implantitis, Peri Implant Mucositis
RecruitingPhase 2
Taurine for the Prevention and Treatment of Radiation-induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma
Oral Mucositis (Ulcerative) Due to Radiation, Nasopharyngeal Carcinoma (NPC)
Recruiting
Home-Use Dual-Light Antibacterial Photodynamic Therapy for Peri-Implant Mucositis in Full-Arch Implant Prostheses
Peri Implant Mucositis, Dental Implant Rehabilitation
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.
Lillian Sung principal investigator
Children's Oncology Group
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Palifermin in people with Gastrointestinal Mucositis and Malignant Neoplasm, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: withdrawn, as of the sponsor's last update on 7 Aug 2018. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Incidence of WHO grade 3 or 4 oral mucositis (time frame: Up to day 32). 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 7 Aug 2018.