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

NCT00482846 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000547155P30CA022453WSU-2006-119
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mucositis; Multiple Myeloma

Keywords

mucositis; drug/agent toxicity by tissue/organ; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis

  Days -5, -4, -3, 2, +1, +2 and +3

Secondary Outcomes (4)

• 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

Study Arms (1)

Palifermin & Melphalen

EXPERIMENTAL

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; Drug: melphalan; Other: questionnaire administration; Procedure: autologous peripheral blood stem cell transplantation; Other: quality-of-life assessment

Interventions

Palifermin BIOLOGICAL

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

Also known as: Kepivance

Palifermin & Melphalen

melphalan DRUG

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;

Also known as: Alkeran

Palifermin & Melphalen

questionnaire administration OTHER

Day -5 to Day +28

Palifermin & Melphalen

autologous peripheral blood stem cell transplantation PROCEDURE

Day 0

Palifermin & Melphalen

quality-of-life assessment OTHER

Day -5 to Day +28

Palifermin & Melphalen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Mucositis; Multiple Myeloma; Drug-Related Side Effects and Adverse Reactions

Interventions

Fibroblast Growth Factor 7; Melphalan

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Muneer H. Abidi, MD

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 4, 2007
• First Posted: June 5, 2007
• Study Start: June 1, 2007
• Primary Completion: October 1, 2011
• Study Completion: September 1, 2012
• Last Updated: April 15, 2014

Record last verified: 2014-04

Locations

US (1)