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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Mucositis, Multiple Myeloma

Intervention / Treatment
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* Biological: Palifermin
* Drug: melphalan
* Other: questionnaire administration
* Procedure: autologous peripheral blood stem cell transplantation
* Other: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palifermin & Melphalen<br>Palifermin 60 mcg/kg/d of the actual body weight unless actual body weight is >40% of the Ideal body weight (IBW), then adjusted body weight (AdBW) will be used for dose calculations - administered on Day - 5,-4, - 3 and then repeated on Day +1, +2 and +3 Dose of Melphalan + Palifermin (Normal Renal Function): All given on Day -2: Dose Level 1- 200 mg/m2 I.V; Dose Level 2- 220 mg/m2 I.V; Dose Level 3- 240 mg/m2 I.V; Dose Level 4- 260 mg/m2 I.V; Dose Level 5- 280 mg/m2 I.V; Dose of Melphalan + Palifermin (Renal Dysfunction CrCl. <60)adm. via I.V.: Dose Level 1- 140 mg/m2; Dose Level 2- 160 mg/m2; Dose Level 3- 180 mg/m2; Dose Level 4- 200 mg/m2; Dose Level 5- 220 mg/m2; | Biological: Palifermin<br>* Palifermin 60 mcg/kg/d of the actual body weight unless actual body weight is >40% of the Ideal body weight (IBW), then adjusted body weight (AdBW) will be used for dose calculations - administered on Day - 5,-4, - 3 and then repeated on Day +1, +2 and +3<br>* Other names: Kepivance;Drug: melphalan<br>* Dose of Melphalan + Palifermin (Normal Renal Function): All given on Day -2: Dose Level 1- 200 mg/m2 I.V; Dose Level 2- 220 mg/m2 I.V; Dose Level 3- 240 mg/m2 I.V; Dose Level 4- 260 mg/m2 I.V; Dose Level 5- 280 mg/m2 I.V; Dose of Melphalan + Palifermin (Renal Dysfunction CrCl. <60)adm. via I.V.: Dose Level 1- 140 mg/m2; Dose Level 2- 160 mg/m2; Dose Level 3- 180 mg/m2; Dose Level 4- 200 mg/m2; Dose Level 5- 220 mg/m2;<br>* Other names: Alkeran;Other: questionnaire administration<br>* Day -5 to Day +28<br>Procedure: autologous peripheral blood stem cell transplantation<br>* Day 0<br>Other: quality-of-life assessment<br>* Day -5 to Day +28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis |  | Days -5, -4, -3, 2, +1, +2 and +3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity |  | Days -5, -4, -3, 2, +1, +2 and +3 | 
| Evaluate the efficacy of Palifermin as a cytoprotective agent in reducing incidence and duration of Grade 3 and 4 mucositis due to high dose Melphlan |  | Day -5 to Day +28 | 
| Overall response |  | At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan | 
| Reduction in incidence and duration of mucositis |  | Days -5 to Day +28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mucositis, drug/agent toxicity by tissue/organ, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma