Phase I Dose Escalation Trial of High Dose Melphalan Conditioning Regimen With Palifermin for Cytoprotection Followed by Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
18 Years
N/A
Both
Mucositis, Multiple Myeloma
Trial Information
Phase I Dose Escalation Trial of High Dose Melphalan Conditioning Regimen With Palifermin for Cytoprotection Followed by Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of high-dose melphalan when administered with
palifermin in patients undergoing autologous peripheral blood stem cell transplantation
for stage II or III multiple myeloma.
Secondary
- Assess overall response (complete and partial response and stable disease) in these
patients at 28 and 100 days post-transplantation.
- Assess the efficacy of palifermin as a cytoprotective agent in reducing incidence and
duration of mucositis in patients treated with this regimen.
- Assess patient-reported outcomes and impact of palifermin on quality of life of these
patients.
- Assess the qualitative and quantitative toxicities of this regimen in these patients.
OUTLINE: This is a dose-escalation study of melphalan. Patients are stratified according to
creatinine clearance (normal vs < 60 mL/min).
Patients receive high-dose melphalan IV on day -2 and palifermin IV on days -5 to -3 and
1-3. Patients undergo autologous peripheral blood stem cell transplantation on day 0.
In each stratum, cohorts of 3-6 patients receive escalating doses of melphalan until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients complete questionnaires about overall health, mouth and throat soreness (MTS), and
activity limitations due to MTS once daily on days -5 to 28.
After completion of study treatment, patients are followed at days 28 and 100 and then
periodically thereafter.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma
- Stage II or III disease
- Must have undergone successful stem cell mobilization (≥ 2.0 x 10^6 CD34+ cells/kg)
- No oral lesions from any other etiology
- No unhealed mucositis from induction treatment
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Amylase and lipase normal
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN
- Creatinine normal (stratum 1 only)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No HIV positivity
- No history of allergic reaction attributed to melphalan
- No uncontrolled illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- No hepatitis B or C positivity
- No prior or concurrent pancreatitis
- No known sensitivity to any of the study drugs, including E. coli-derived products
PRIOR CONCURRENT THERAPY:
- Prior bone marrow or stem cell transplantation allowed
- No prior palifermin
- More than 30 days since prior investigational agents
- No concurrent dialysis
- No concurrent amifostine
- No concurrent prophylactic oral cryotherapy during melphalan administration
- No concurrent mouthwash solutions containing any of the following:
- Chlorhexidine
- Hydrogen peroxide
- Diphenhydramine hydrochloride
- No concurrent recombinant interleukin-11 or sargramostim (GM-CSF)
- No concurrent sucralfate in suspension form
- Sucralfate tablets allowed
- No concurrent povidone-iodine rinses
- No concurrent glutamine as a prophylactic agent for mucositis
- No other concurrent investigational agents
- No concurrent antithymocyte globulin suppression or alemtuzumab
- No concurrent rituximab
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis
Outcome Time Frame:
Days -5, -4, -3, 2, +1, +2 and +3
Safety Issue:
Yes
Principal Investigator
Muneer H. Abidi, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000547155
NCT ID:
NCT00482846
Start Date:
June 2007
Completion Date:
October 2012
Related Keywords:
- Mucositis
- Multiple Myeloma
- mucositis
- drug/agent toxicity by tissue/organ
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Mucositis
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
