Melphalan and Palifermin in Treating Patients Undergoing An Autologous Peripheral Stem Cell Transplant for Stage II or III 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.

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