The purpose of the research study is to determine the response rates when Revlimid® is combined with Doxil® and Dexamethasone (Dd-R) in newly diagnosed Multiple Myeloma. The study will also evaluate the side effects caused by the combination of these three drugs. This therapy is investigational in the treatment of Multiple Myeloma. Revlimid® is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Revlimid® is approved by the Food and Drug Administration (FDA) for specific types of myelodysplastic syndrome (MDS) and Multiple Myeloma, two different types of blood cancer. It is currently being tested in a variety of other cancer conditions. In this case it is considered experimental. Doxil® is a form of chemotherapy. It is approved by the FDA for the treatment of relapsed/ refractory Multiple Myeloma in combination with Velcade. Dexamethasone is a steroid. It is also approved by the FDA, but not for the treatment of Multiple Myeloma. It is considered a standard part of most myeloma therapies for newly diagnosed patients.
Induction Phase: Newly diagnosed multiple myeloma patients with active disease, will be treated with Dd-R as outlined below: All patients will also receive Levaquin 500 mg by mouth (PO) every day (QD) \[or if allergic receive amoxicillin 250 mg PO twice a day (BID)\], acyclovir 400 mg PO BID or Valacyclovir 500 mg BID and aspirin 81 mg PO QD daily while receiving Dd-R. Aspirin will continue through maintenance. For patients who cannot tolerate aspirin, low molecular weight heparin or therapeutic doses of coumadin may be used in place of aspirin. * Doxil® 30 mg/m\^2 on day # 1 to be repeated every 28 days * Dexamethasone 40 mg per day for 4 days (days 1-4) every 28 days * Revlimid® 25 mg PO daily on days 1-21, followed by 7 days of no therapy, repeated every 28 days Maintenance Therapy: Patients who complete the induction regimen or those who complete at least 2 cycles of the induction regimen and not showing evidence of progressive disease but cannot tolerate any further chemotherapy could be started on maintenance therapy as follows: * Revlimid® 15 mg or 25 mg\* PO daily on days 1-21, followed by 7 days of no therapy, repeated every 28 days Patients will start maintenance therapy at the dexamethasone dose that was tolerated at the completion of the induction phase. \*The starting Revlimid® dose for maintenance will be either 15 mg or 25 mg, which will be determined based on whether specific criteria are met on scheduled Day 1. * Dexamethasone 40 mg per day for 4 days (days 1-4) every 28 days All participants will also receive aspirin 81 mg PO QD daily while receiving maintenance. For patients who cannot tolerate aspirin, low molecular weight heparin or therapeutic doses of coumadin may be used in place of aspirin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
57
25 mg orally on days 1-21
40 mg/m\^2 intravenously on day 1 (reduced to 30 mg/m\^2 after the initial 29 patients were treated)
40 mg orally on days on 1-4
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Overall Response Rate (ORR) - Percentage of Participants With Partial Response or Better With Induction Regimen
ORR assessed using International Myeloma Working Group Response Definitions. Partial Remission (PR): A greater than 50% reduction in the serum paraprotein, and if present, a greater than 90% reduction in the urine M protein excretion. Patients must also have a decrease by 50% in the size of soft tissue plasmacytoma. If serum and urine M protein are not measurable, a 50% or greater decreased in the difference of the involved and uninvolved free light chain. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
Time frame: 24 Months
Percentage of Participants With Very Good Partial Remission (VGPR) or Better
Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction Dd-R as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
Time frame: 24 Months
Median Progression Free Survival (PFS) in Months
PFS: Time from study entry to progression/relapse or death from study entry to death of any cause, assessed using International Myeloma Working Group Response Definitions. Progressive Disease (PD): One of the following criteria must be met: a. Increase of 25% or greater in serum M protein (absolute increase greater or equal to 0.5g/dl); b. Increase of 25% or greater in urine M protein (absolute increase greater than 200 mg/24h); c. Increase of 25% or greater in the difference between the involved and uninvolved free light chain (absolute increase greater than 10 mg/dl); d. Increase of 25% or greater in bone marrow plasma cell percentage (absolute percent greater than 5% in case the patient was in CR and 10% otherwise); i.e. Definite development of new bone lesions or soft tissue plasmacytomas, or increase in the size of existing plasmacytomas by greater or equal to 25%. Development of hypercalcemia (serum calcium \> 11.5 mg/dl) attributable only to the plasma cell dyscrasia.
Time frame: 24 Months
2 Year Overall Survival (OS) Rate
Percentage of participants with Overall Survival in response to Dd-R in newly diagnosed multiple myeloma patients with active disease. Overall survival is time from study entry to death of any cause.
Time frame: 24 Months
Occurrence of Induction Toxicities
Tolerability of full dose Revlimid® with full dose Doxil® in combination with reduced schedule dexamethasone was to be assessed during Cycle 1 and at the start of Cycle 2 using, whenever possible, the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0. Due to increased neutropenia and fatigue, toxicities were reviewed after the first 29 participants were enrolled.
Time frame: 24 Months
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