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

Primary Purpose

Mucositis, Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Palifermin

melphalan

questionnaire administration

autologous peripheral blood stem cell transplantation

quality-of-life assessment

About this trial

This is an interventional supportive care trial for Mucositis focused on measuring mucositis, drug/agent toxicity by tissue/organ, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Palifermin & Melphalen

Arm Description

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;

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Dose-limiting toxicity

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

Overall response

Reduction in incidence and duration of mucositis

Full Information

NCT ID

NCT00482846

First Posted

June 4, 2007

Last Updated

April 14, 2014

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00482846

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

October 2011 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucositis, Multiple Myeloma

Keywords

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

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Palifermin & Melphalen

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Palifermin

Other Intervention Name(s)

Kepivance

Intervention Description

Intervention Type

Drug

Intervention Name(s)

melphalan

Other Intervention Name(s)

Alkeran

Intervention Description

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

Other

Intervention Name(s)

questionnaire administration

Intervention Description

Day -5 to Day +28

Intervention Type

Procedure

Intervention Name(s)

autologous peripheral blood stem cell transplantation

Intervention Description

Day 0

Intervention Type

Other

Intervention Name(s)

quality-of-life assessment

Intervention Description

Day -5 to Day +28

Primary Outcome Measure Information:

Title

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

Time Frame

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

Secondary Outcome Measure Information:

Title

Dose-limiting toxicity

Time Frame

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

Title

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

Title

Overall response

Time Frame

At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan

Title

Reduction in incidence and duration of mucositis

Time Frame

Days -5 to Day +28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Muneer H. Abidi, MD

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Barbara Ann Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201-1379

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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