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
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
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Keratinocyte growth factors, such as palifermin, may help prevent symptoms of mucositis, or mouth sores, in patients receiving melphalan before a peripheral stem cell transplant for multiple myeloma.
PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given together with palifermin in treating patients undergoing an autologous peripheral stem cell transplant for stage II or stage III multiple myeloma.
OBJECTIVES:
Primary
Secondary
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
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:
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:
No concurrent recombinant interleukin-11 or sargramostim (GM-CSF)
No concurrent sucralfate in suspension form
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