Multiple Myeloma
Conditions
Brief summary
This study is being done to find out if the combination of VelcadeTM with melphalan and dexamethasone (VMD) will be as effective, or even more effective as it is in combination with thalidomide and dexamethasone (VTD).
Detailed description
A new drug (bortezomib \[VelcadeTM PS-341\]) has been shown in recent studies to be effective in subjects with advanced multiple myeloma. There is also research that shows this drug may be even more effective when used in combination with other drugs that have been used to treat myeloma for many years (melphalan, thalidomide, and dexamethasone). This study is being done to find out if the combination of VelcadeTM with melphalan and dexamethasone (VMD) will be as effective, or even more effective as it is in combination with thalidomide and dexamethasone (VTD).
Interventions
DRUGVelcade, Thalidomide, and Dexamethasone
Velcade - Into vein (IV) Days 1, 4, 8, 11 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles Thalidomide - By Mouth Days 1-28 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles
DRUGVelcade, Melphalan, and Dexamethasone
Velcade - Into vein (IV) Days 1, 4, 8, 11 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles
Sponsors
University of Arkansas
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of histologically documented MM previously enrolled on UARK 98-026 with relapsed or progressive disease after at least one autologous transplant. * Patient has measurable disease in which to capture response, defined as: * Serum M-protein level \> 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis * Urinary M-protein excretion \> 200 mg/24 hrs * Bone marrow plasmacytosis of \> 30percent by bone marrow aspirate and/or biopsy * Serum Free Light Chains (By the Freelite test) \> 10 mg/dL with an abnormal kappa/lambda ration. * 50percent increase in size of lytic and/or focal lesions or development of new lesions recognized by radiographic studies. * Performance status of 2 as per SWOG scale, unless PS of 3-4 based solely on bone pain. * Patients must have a platelet count 50,000/mm3, unless the low platelet count is due to documented (\>30 percent) extensive myeloma infiltration of the bone marrow. * Patients must have adequate renal function defined as serum creatinine \< 2.5 mg/dl. * Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin \< 2 x the upper limit of normal. * Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Male or female adults of at least 18 years of age. * Patients must have signed and IRB-approved written informed consent form and demonstrate willingness to meet follow-up schedule and study procedure obligations * \> 5 x 106 CD34 cells/kg in storage strongly desired, but not mandated
Exclusion criteria
* Not previously enrolled on UARK 98-026. * Has received salvage therapy after coming off UARK 98-026. * Evidence of POEMS Syndrome.. * Significant neurotoxicity interfering with ADL. * Platelet count \< 50,000/mm3 * Clinically significant hepatic dysfunction as noted by bilirubin or AST \>3 times the upper normal limit or clinically significant concurrent hepatitis. * New York Hospital Association (NYHA) Class III or Class IV heart failure. * Myocardial infarction within the last 6 months. * Truly non-secretory MM (no increase in serum free-light chains) in the absence of bone marrow plasmacytosis and MRI-defined focal lesions with CT-FNA-proven MM * Uncontrolled, active infection requiring IV antibiotics. * Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias. * Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol. * Pregnant or potential for pregnancy. Women of childbearing potential will have a pregnancy test at screening, and will be required to use a medically approved contraceptive method. Pregnancy testing will be performed prior to administration of each dose of study drug. * Breast-feeding women may not participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Survival With Velcade/Melphalan/Dexamethasone Treatment vs. Participant Survival With Velcade/Thalidomide/Dexamethasone Treatment | 24 months | due to low accrual rates, no analyses was done to compare the new combination of Velcade/Melphalan/Dexamethasone vs. Velcade/Thalidomide/Dexamethasone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Velcade, Thalidomide, and Dexamethasone Velcade 1.0 mg/m\^2 Velcade 1.3 mg/m\^2 D1,4, 8, 11 (x 6 cycles, then 1.0 mg/m\^2 (for cycles 7-12) Thalidomide 100 mg D1-28 Dexamethasone 20 mg D1-4 and 8-11 | 3 |
| VMD With Melphalan Dose Escalation VMD:
Velcade 1.3 mg/m\^2 D1, 4, 7, 10 (x6 mo, then 1.0 mg/m\^2) Melphalan 4 (6, 8, 10) mg/m\^2 D1, 4, 7, 10 dose escalation Dexamethasone 20 mg 1-4 and 7-10 | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | study stopped | 2 | 2 |
Baseline characteristics
| Characteristic | Velcade, Thalidomide, and Dexamethasone | VMD With Melphalan Dose Escalation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 5 | 0 / 5 |
| serious Total, serious adverse events | 1 / 5 | 1 / 5 |
Outcome results
Primary
Participant Survival With Velcade/Melphalan/Dexamethasone Treatment vs. Participant Survival With Velcade/Thalidomide/Dexamethasone Treatment
due to low accrual rates, no analyses was done to compare the new combination of Velcade/Melphalan/Dexamethasone vs. Velcade/Thalidomide/Dexamethasone
Time frame: 24 months