Cancer, Multiple Myeloma
Conditions
Keywords
Cancer, Multiple Myeloma, Peripheral Blood Stem Cell Transplant
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.
Interventions
DRUGBortezomib
Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.
DRUGMelphalan
All patients received melphalan (100 mg/m\^2/day × 2; days -3 and -2), for a total dose of 200 mg/m\^2.
PROCEDUREAutologous PBSC Transplant
Day 0 consists of the stem cell infusion.
Sponsors
Millennium Pharmaceuticals, Inc.
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care * Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements *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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib Before HD Melphalan All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2 | 19 |
| Bortezomib After HD melphalanAll patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2 | 20 |
| Total | 39 |
Baseline characteristics
| Characteristic | Bortezomib After HD melphalanAll | Bortezomib Before HD Melphalan | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 28 Participants |
| Age Continuous | 58.75 years STANDARD_DEVIATION 8.05 | 58.32 years STANDARD_DEVIATION 7.92 | 58.54 years STANDARD_DEVIATION 7.88 |
| Region of Enrollment United States | 20 participants | 19 participants | 39 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 18 / 20 |
| serious Total, serious adverse events | 4 / 19 | 2 / 20 |
Outcome results
Primary
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.
Time frame: Day 30 after transplant
Population: As per the protocol
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bortezomib Before HD Melphalan | Safety and Engraftment | Median time for platelet recovery | 16 days |
| Bortezomib Before HD Melphalan | Safety and Engraftment | Median time for neutrophil recovery | 12 days |
| Bortezomib After HD melphalanAll | Safety and Engraftment | Median time for platelet recovery | 16 days |
| Bortezomib After HD melphalanAll | Safety and Engraftment | Median time for neutrophil recovery | 12 days |
Secondary
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.
Time frame: 100 days after transplant
Population: As per the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib Before HD Melphalan | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | Partial Response | 6 participants |
| Bortezomib Before HD Melphalan | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | Complete response (CR) | 2 participants |
| Bortezomib Before HD Melphalan | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | VGPR-Very good partial remission | 9 participants |
| Bortezomib After HD melphalanAll | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | VGPR-Very good partial remission | 11 participants |
| Bortezomib After HD melphalanAll | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | Partial Response | 7 participants |
| Bortezomib After HD melphalanAll | Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. | Complete response (CR) | 6 participants |