Melphalan & Palifermin Followed by Peripheral Blood Stem Cell Transplant in Treating Pts w/Stage II-III Multiple Myeloma

• Dose-limiting toxicity of palifermin according to Common Terminology Criteria v 3.0 [ Time Frame: Up to 20 days after completion of treatment ] [ Designated as safety issue: Yes ]
• Grade IV mucositis and diarrhea related to melphalan [ Time Frame: Days -2, 0, and 1-28 ] [ Designated as safety issue: Yes ]
• Overall response [ Time Frame: Days 28 and 100 ] [ Designated as safety issue: No ]
• Reduction in the incidence and duration of grade III/IV mucositis [ Time Frame: Days -5 to 28 ] [ Designated as safety issue: No ]
• Quality of life assessments [ Time Frame: Days -5, 0, and 1-28 ] [ Designated as safety issue: No ]

This pilot phase I trial studies the side effects and the best dose of melphalan when given together with palifermin followed by peripheral blood stem cell transplant (PBSCT) in treating patients with stage II-III multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Palifermin may help prevent symptoms of mucositis, or mouth sores, in patients receiving melphalan followed by a PBSCT

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of melphalan in patients with normal and abnormal renal function undergoing autologous stem cell transplants for myeloma when treated with palifermin to prevent mucositis.

SECONDARY OBJECTIVES:

I. To assess overall response (compete response [CR], partial response [PR], stable disease [SD]) at D+28 and D+100 after autologous transplant when treated with combination of palifermin and Melphalan.

II. To evaluate the efficacy of Palifermin as a cytoprotective agent in reducing incidence and duration of Grade 3 and 4 mucositis due to high dose Melphalan.

III. To assess patient reported outcomes and impact of using palifermin on quality of life in the post transplant duration.

IV. To assess the qualitative and quantitative toxicities associated with this regimen.

OUTLINE: This is a dose-escalation study of melphalan.

CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) on day -2 and palifermin IV on days -5 to -3 and 1-3.

TRANSPLANTATION: Patients undergo autologous PBSCT on day 0.

After completion of study treatment, patients are followed up at days 28 and 100, and then periodically thereafter.

• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

• Drug: melphalan
  Given IV
  Other Names:

  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
• Biological: palifermin
  Given IV
  Other Names:

  • growth factor, recombinant human keratinocyte
  • Kepivance
  • keratinocyte growth factor, recombinant human
  • recombinant human keratinocyte growth factor
  • rhKGF
• Procedure: peripheral blood stem cell transplantation
  Undergo autologous PBSCT
  Other Names:

  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
• Procedure: autologous hematopoietic stem cell transplantation
  Undergo autologous PBSCT

Inclusion Criteria:

Patients with Stage II/III myeloma who meet the institutional criteria for undergoing high-dose chemotherapy and autologous transplant for multiple myeloma will be eligible for this study; patients in the abnormal renal function group should have no other organ dysfunction that does not meet institutional criteria Minimum of 2.0 x 10^6 cluster of differentiation (CD) 34+ cells/kg cryopreserved and to be transplanted Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect if she is pregnant while participating in this study, she should inform her physician immediately Ability to understand and the willingness to sign a written informed consent Women patients must have a negative human immunodeficiency virus (HIV) and pregnancy test; these tests will be performed with pre-transplant work up for eligibility/clearance Patients in Stratum 1 should have a normal serum creatinine and a normal amylase and lipase in both Strata at baseline Patients with prior bone marrow/stem cell transplantation will be eligible for the study

Exclusion Criteria:

Baseline oral lesions from any other etiology or unhealed mucositis from induction treatment Patients may not be receiving any other investigational agents 30 days prior to registration on this protocol History of allergic reactions attributed to Melphalan Total bilirubin > 1.5 x upper limit of normal Transaminase > 3 x normal Uncontrolled inter current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, seropositive for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or psychiatric illness/social situations that would limit with study requirements Patients who do not meet institutional criteria for autologous stem cell transplant (Exception: creatinine clearance [CrCl]: < 60 for stratum 2) Patients undergoing dialysis will not be allowed on this study History of or current diagnosis of pancreatitis Subject or partner of subject is not using or refuses to use adequate contraceptive precautions Subject has known sensitivity to any of the products to be administered during dosing including Escherichia coli-derived products Prior use of palifermin