Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

Phase 1

Terminated

Conditions: Cancer
Multiple Myeloma

Interventions: Drug: Bortezomib
Drug: Melphalan
Procedure: Autologous PBSC Transplant

Registration Number: NCT00793650

Lead Sponsor: Emory University

Brief Summary: The goal of this study is to evaluate the safety of melphalan and autologous PBSCT (peripheral blood stem cell transplantation - stem cells that come from your own body) in combination with bortezomib, a new FDA approved drug used to treat myeloma.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 39

Inclusion Criteria

Patients with multiple myeloma who are eligible for an autologous peripheral blood progenitor transplant
Male and female subjects between the age of 18 and 70 years.
Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care
Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements
Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Male subjects agrees to use an acceptable method for contraception for the duration of the study.
Biopsy proven diagnosis of multiple myeloma from bone marrow aspirate and biopsy prior to study initiation
Patient has achieved less than 90% disease reduction from previous treatment prior to transplant (as measured by serum or urine protein electrophoresis) and has more than 5% plasma cells in the bone marrow, or patient has progressed and has more than 5% plasma cells in the bone marrow.
Karnofsky Performance Status score of ≥ 60%
Patient has met the following laboratory requirements prior to Day -4
Platelet count ≥ 50, 000/mm3
Absolute Neutrophil Count ≥ 500/mm3
Hemoglobin ≥ 10 g/dL (transfusion allowed to meet this criterion)
Calculated creatinine clearance ≥ 30mL/min
Toxic effects of previous therapy or surgery resolved to Grade 2 or better

Exclusion Criteria

Unsupportable anemia with < 10b/dL
Patient has a calculated or measured creatinine clearance of < 30mL/min within 14 days before enrollment
Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
Patient has hypersensitivity to bortezomib, boron or mannitol
Patient has had an allergic reaction to melphalan or chlorambucil
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Patient has received other investigational drugs with 14 days before enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Cardiac or pulmonary dysfunction such that patients do not meet institutional pre-transplant evaluation criteria
Known central nervous system involvement or suspicion of involvement with Myeloma
Other active malignancies (with the exception of basal and squamous cell skin cancer) within 5 years of study entry. Patients with treated prostate or cervical cancer in situ who are 2 or more years from therapy and remain free of disease may be entered into the study at the investigator's discretion.
Known to be HIV positive, HIV-1 positive

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bortezomib before Melphalan	Autologous PBSC Transplant	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours before melphalan.
Bortezomib after Melphalan	Autologous PBSC Transplant	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours after melphalan.
Bortezomib before Melphalan	Bortezomib	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours before melphalan.
Bortezomib before Melphalan	Melphalan	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours before melphalan.
Bortezomib after Melphalan	Bortezomib	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours after melphalan.
Bortezomib after Melphalan	Melphalan	Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours after melphalan.

Primary Outcome Measures

Name	Time	Method
Safety and Engraftment	Day 30 after transplant	Peripheral blood progenitor cells were collected with either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10\^6/kg CD34+ cells (range, 2.3-65) as their transplant graft.

Secondary Outcome Measures

Name	Time	Method
Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant.	100 days after transplant	CR :Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24 hour. Partial Response:\>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200mg per 24 hour.