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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Muneer Abidi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00482846
First received: June 4, 2007
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Mucositis
Multiple Myeloma
Biological: Palifermin
Drug: melphalan
Other: questionnaire administration
Procedure: autologous peripheral blood stem cell transplantation
Other: quality-of-life assessment
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis [ Time Frame: Days -5, -4, -3, 2, +1, +2 and +3 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose-limiting toxicity [ Time Frame: Days -5, -4, -3, 2, +1, +2 and +3 ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Day -5 to Day +28 ] [ Designated as safety issue: Yes ]
  • Overall response [ Time Frame: At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan ] [ Designated as safety issue: No ]
  • Reduction in incidence and duration of mucositis [ Time Frame: Days -5 to Day +28 ] [ Designated as safety issue: Yes ]

Enrollment: 38
Study Start Date: June 2007
Study Completion Date: September 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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;

Biological: 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
Other Name: Kepivance
Drug: 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;

Other Name: Alkeran
Other: questionnaire administration
Day -5 to Day +28
Procedure: autologous peripheral blood stem cell transplantation
Day 0
Other: quality-of-life assessment
Day -5 to Day +28

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00482846

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Muneer H. Abidi, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Muneer Abidi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00482846     History of Changes
Other Study ID Numbers: CDR0000547155, P30CA022453, WSU-2006-119
Study First Received: June 4, 2007
Last Updated: April 14, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
mucositis
drug/agent toxicity by tissue/organ
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Mucositis
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Mouth Diseases
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Stomatognathic Diseases
Vascular Diseases
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014