Clinical trial NCT00482846: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mucositis
Multiple Myeloma
Keywords: mucositis
drug/agent toxicity by tissue/organ
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-05
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis
timeFrame: Days -5, -4, -3, 2, +1, +2 and +3
Secondary outcomes:
measure: Dose-limiting toxicity
timeFrame: Days -5, -4, -3, 2, +1, +2 and +3
measure: 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
timeFrame: Day -5 to Day +28
measure: Overall response
timeFrame: At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan
measure: Reduction in incidence and duration of mucositis
timeFrame: Days -5 to Day +28
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Muneer H. Abidi, MD
role: PRINCIPAL_INVESTIGATOR
References: