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

Study Overview
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Brief Summary
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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.

Official Title
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Combination High Dose Melphalan and Autologous PBSC Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

Conditions
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Cancer, Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Melphalan
* Procedure: Autologous PBSC Transplant


Participation Criteria
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Eligibility Criteria
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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 Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements Female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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bortezomib before Melphalan<br>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. | Drug: Bortezomib<br>* Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.<br>* Other names: Bortezomib or Velcade;Drug: Melphalan<br>* All patients received melphalan (100 mg/m^2/day × 2; days -3 and -2), for a total dose of 200 mg/m^2.<br>* Other names: Bortezomib or Velcade;Procedure: Autologous PBSC Transplant<br>* Day 0 consists of the stem cell infusion.<br>|
| Active Comparator: Bortezomib after Melphalan<br>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. | Drug: Bortezomib<br>* Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.<br>* Other names: Bortezomib or Velcade;Drug: Melphalan<br>* All patients received melphalan (100 mg/m^2/day × 2; days -3 and -2), for a total dose of 200 mg/m^2.<br>* Other names: Bortezomib or Velcade;Procedure: Autologous PBSC Transplant<br>* Day 0 consists of the stem cell infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Engraftment | 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. | Day 30 after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 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. | 100 days after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Multiple Myeloma, Peripheral Blood Stem Cell Transplant