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

NCT ID: NCT00482846

Last Updated: 2014-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2012-09-30

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.

Detailed Description

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.

Conditions

Mucositis; Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Palifermin & Melphalen

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;

Group Type: EXPERIMENTAL

Palifermin

Intervention Type: 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

melphalan

Intervention Type: 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;

questionnaire administration

Intervention Type: OTHER

Day -5 to Day +28

autologous peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Day 0

quality-of-life assessment

Intervention Type: OTHER

Day -5 to Day +28

Interventions

Palifermin

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

Intervention Type: BIOLOGICAL

melphalan

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;

Intervention Type: DRUG

questionnaire administration

Day -5 to Day +28

Intervention Type: OTHER

autologous peripheral blood stem cell transplantation

Day 0

Intervention Type: PROCEDURE

quality-of-life assessment

Day -5 to Day +28

Intervention Type: OTHER

Other Intervention Names

Kepivance; Alkeran

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Muneer Abidi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Muneer H. Abidi, MD

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-2006-119

Identifier Type: -

Identifier Source: secondary_id

CDR0000547155

Identifier Type: -

Identifier Source: org_study_id

NCT01654744

Identifier Type: -

Identifier Source: nct_alias