Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
Brief summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide, dexamethasone, and bortezomib may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide and dexamethasone with or without bortezomib works in treating patients with multiple myeloma.
Detailed description
OBJECTIVES: * Determine the efficacy and safety of bortezomib, pegylated doxorubicin hydrochloride liposome, and dexamethasone followed by thalidomide and dexamethasone with or without bortezomib in patients with symptomatic high-risk or primary resistant multiple myeloma. OUTLINE: Patients receive BDD comprising bortezomib IV on days 1, 4, 8, and 11; pegylated doxorubicin hydrochloride liposome IV over 60-90 minutes on day 4; and oral dexamethasone on day 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving response to BDD receive oral thalidomide on days 1-28 and oral dexamethasone on days 1-4, 9-12, and 17-20. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing stable or progressive disease on BDD receive oral thalidomide on days 1-28; oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, 12, and 17-21; and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGbortezomib
DRUGdexamethasone
DRUGpegylated liposomal doxorubicin hydrochloride
DRUGthalidomide
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically and serologically confirmed multiple myeloma meeting one of the following criteria: * High-risk myeloma, defined as symptomatic International Staging System (ISS) stage 2 or 3 multiple myeloma * Soft-tissue involvement with myeloma in the form of a soft-tissue plasmacytoma * Extension of a plasmacytoma into soft tissues * Primary resistant myeloma, defined as unchanged or progressive myeloma despite two courses of standard treatment * No ISS stage 1 multiple myeloma without soft-tissue involvement * No smoldering myeloma PATIENT CHARACTERISTICS: * ECOG performance status 0-3 * Life expectancy \> 16 weeks * Absolute granulocyte count ≥ 1,500/mm³ (unless low granulocyte counts are due to multiple myeloma) * Platelet count ≥ 100,000/mm³ (unless low platelet counts are due to multiple myeloma) * Bilirubin ≤ 2.0 mg/dL * AST and ALT \< 3 times upper limit of normal (ULN) * Alkaline phosphatase \< 3 times ULN * LVEF ≥ 50% by MUGA or ECHO * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception 4 months prior to, during, and for 4 weeks after completion of study treatment * No active thromboembolic disease on anticoagulation * No active angina or myocardial infarction within the past 6 months * No pre-existing neuropathy or sensory or neuropathic pain ≥ grade 2 * No concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix * Prior malignancies that have not required antitumor treatment within the past 24 months allowed * Patients with a history of stage I or II (T1a/b) prostate cancer (detected incidentally at transurethral resection of prostate \[TURP\] and comprising \< 5% of resected tissue) allowed if the prostate-specific antigen has remained normal since TURP * No known HIV positivity or AIDS-related illness * No other medical condition or reason that, in the opinion of the investigator, would preclude study compliance * No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or to components of pegylated doxorubicin hydrochloride liposome, bortezomib, boron, or mannitol PRIOR CONCURRENT THERAPY: * Prior radiotherapy allowed * No more than 2 courses of prior initial chemotherapy for multiple myeloma * No prior bortezomib * No prior high-dose steroids (not including taper) for more than 1 month in duration for emergent indications, such as hypercalcemia or life-threatening lesions (e.g., spinal cord compromise) (in high-risk patients)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response | 2 years | The response of myeloma to BDDTD will be assessed by standard electrophoretic and immunofixation tests of blood and urine for a monoclonal protein (M protein), and bone marrow aspirate and biopsy. These tests will be performed at enrollment and at the conclusion of therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination Therapy Combination therapy with bortezomib, pegylated liposomal doxorubicin and dexamethasone (BDD) followed by either thalidomide and dexamethasone (TD) or bortezomib, thalidomide and dexamethasone in patients with symptomatic untreated high-risk or primary resistant multiple myeloma. Three cycles of BDD will be administered. Patients who respond after three cycles will receive two cycles of TD. Patients with stable or progressive disease after three cycles of BDD receive two cycles of bortezomib, thalidomide and dexamethasone. If at any point during the study a patient achieves a complete response (CR), the patient will be given the option to discontinue treatment on-study. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Not Treated | 1 |
Baseline characteristics
| Characteristic | Combination Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 45 |
| serious Total, serious adverse events | 22 / 45 |
Outcome results
Primary
Disease Response
The response of myeloma to BDDTD will be assessed by standard electrophoretic and immunofixation tests of blood and urine for a monoclonal protein (M protein), and bone marrow aspirate and biopsy. These tests will be performed at enrollment and at the conclusion of therapy.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Therapy | Disease Response | Complete Response | 10 participants |
| Combination Therapy | Disease Response | Near Complete Response | 8 participants |
| Combination Therapy | Disease Response | Partial Response | 10 participants |
| Combination Therapy | Disease Response | Stable Disease | 2 participants |
| Combination Therapy | Disease Response | Progression of Disease | 3 participants |
| Combination Therapy | Disease Response | Very Good Partial Response | 7 participants |