Multiple Myeloma
Conditions
Keywords
Temsirolimus, Bortezomib
Brief summary
The purpose of this research study is to determine the safety of CCI-779 (Temsirolimus) and bortezomib (Velcade), and the highest dose of this drug that can be given to people safely. We will also be looking at how the combination of the two drugs may work against multiple myeloma. CCI-779 (Temsirolimus) is a drug that appears to stop myeloma cells from growing.
Detailed description
* Since we are looking for the highest dose of CCI-779 (Temsirolimus) given in combination with bortezomib (Velcade) that can be given to people without causing the most serious or unmanageable side effects, not everyone who participates in this study will be receiving the same amount of either drug. * During the study treatment, participants will be given some medications to decrease the chance they they will have an allergic reaction to CCI-779 (Temsirolimus). After these drugs are given, participants will be receive bortezomib (Velcade) by injection followed by an injection of CCI-779 (Temsirolimus). These drugs wil be given once a week for four weeks (on Days 1, 8, 15, and 22). On the fifth week (Day 29), participants will be given only CCI-779 along with the drugs to decrease the chance of an allergic reaction. * The cycle will last 35 days and will occur twice before the doctor evaluates for response. The cycles will be repeated for up to 8 cycles as long as the participant does not have any severe or unmanageable side effects and the disease is responding to treatment. * While receiving study treatment, participants will be seen at the clinic at the start of each cycle for the following: complete physical examination, blood work, urine collection, x-ray of bones (if study doctor deems necessary) and an electrocardiogram (prior to treatment and at the end of treatment) * A bone skeletal survey will be performed at the end of treatment to measure the size of the participants tumors. * After 8 cycles of treatment or if the participant has ended treatment, more tests will be performed. A physical exam, blood work, urine collection, skeletal survey, electrocardiogram, bone marrow biopsy and aspirate will be performed.
Interventions
DRUGCCI-779
Given by injection once a week for 5 weeks (5 weeks equals one cycle) for up to 8 cycles
DRUGBortezomib
Given by injection once a week for 4 weeks (a cycle equals 5 weeks) for up to 8 cycles
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Millennium Pharmaceuticals, Inc.
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Must have received prior therapy for their myeloma and have relapsed and/or relapsed/refractory multiple myeloma * Monoclonal protein in the serum of greater than or equal to 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200mg/24 hours, or measurable light chains by free light chain assay of greater than or equal to 10mg/dl, or measurable plasmacytoma * ECOG Performance Status 0, 1 or 2 * Laboratory values as outlined in the protocol
Exclusion criteria
* Uncontrolled infection * Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma. * Pregnant or nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational within 14 days before enrollment * Known to be HIV positive * Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities * Hypersensitivity to bortezomib, boron or mannitol * Serious medical or psychiatric illness likely to interfere with participation in this clinical trial * Patients who may need or are receiving live vaccines for immunization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity. Number of Patients With Specific Toxicities Are Reported. | 10 months | Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma. |
| Best Response to Combination Treatment | 10 months | Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 10 months | Median time to progression or death |
Countries
United States
Participant flow
Recruitment details
Between June, 2007, and December, 2009, we enrolled patients into our open-label, dose-escalation study at three centres in the USA (Dana-Farber Cancer Institute, Boston, MA; Washington University, St Louis, MO; and the University of Michigan, Ann Arbor, MI).
Participants by arm
| Arm | Count |
|---|---|
| CCI779 and Bortezomib Phase I CCI779 and Bortezomib Phase I part of this Phase I/II study. | 20 |
| CCI779 and Bortezomib Phase II CCI779 and Bortezomib Phase II part of this Phase I/II study | 43 |
| Total | 63 |
Baseline characteristics
| Characteristic | CCI779 and Bortezomib Phase I | CCI779 and Bortezomib Phase II | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 20 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 23 Participants | 38 Participants |
| Region of Enrollment United States | 20 participants | 43 participants | 63 participants |
| Sex: Female, Male Female | 7 Participants | 24 Participants | 31 Participants |
| Sex: Female, Male Male | 13 Participants | 19 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 20 | 34 / 43 |
| serious Total, serious adverse events | 13 / 20 | 25 / 43 |
Outcome results
Primary
Best Response to Combination Treatment
Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma
Time frame: 10 months
Population: All patients included in analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CCI779 Toxicity Phase I | Best Response to Combination Treatment | 10 percentage of patients |
| CCI779 Toxicity Phase II | Best Response to Combination Treatment | 33 percentage of patients |
Comparison: Phase I part of this phase I/II study90% CI: [0.02, 0.28]
Comparison: Phase II part of this phase I/II study.90% CI: [0.21, 0.47]
Primary
Toxicity. Number of Patients With Specific Toxicities Are Reported.
Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma.
Time frame: 10 months
Population: Any patient who was treated was included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CCI779 Toxicity Phase I | Toxicity. Number of Patients With Specific Toxicities Are Reported. | 90 percentage of patients |
| CCI779 Toxicity Phase II | Toxicity. Number of Patients With Specific Toxicities Are Reported. | 79 percentage of patients |
Comparison: Single Arm Study90% CI: [0.72, 0.98]
Comparison: Phase II toxicity90% CI: [0.66, 0.89]
Secondary
Progression-Free Survival
Median time to progression or death
Time frame: 10 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CCI779 Toxicity Phase I | Progression-Free Survival | 5.7 month |
| CCI779 Toxicity Phase II | Progression-Free Survival | 5.0 month |