Official Title: “Phase II Study of Pegylated Liposomal Doxorubicin (Doxil®), Low Frequency Dexamethasone and Revlimid® (Dd-R) in Newly Diagnosed Multiple Myeloma”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2010

Induction treatment Cycles 1 - 8 (Each cycle =28 days)

For Cycles 1-8: - Patients will be given Doxil® in the clinic through an IV - Patients will take 25mg of Revlimid® once a day by mouth on days 1-21 followed by 7 days of rest every 28 days. They will swallow the Revlimid® capsules whole with water, not break, chew or open the capsules. If they miss a dose of lenalidomide, they will take it as soon as they remember on the same day. If they miss taking their dose for the entire day, they will take their regular dose the next scheduled day (will NOT take double the regular dose to make up for the missed dose). - Patients will take Dexamethasone by mouth once a day on Days 1-4 of each 28 day cycle.

Dexamethasone should always be taken in the morning with food. - Patients will also take an aspirin (81 mg ) daily for 28 days to prevent blood clots. - Patients will take amoxicillin (or if allergic, Ciprofloxacin), an antibiotic to prevent infection, by mouth twice a day. - Patients will take acyclovir (or Valacyclovir), a drug to prevent herpes viral infection by mouth twice a day

Maintenance therapy:

Based on the patient's response to induction therapy, patients may proceed to maintenance therapy which consists of Revlimid® and Dexamethasone. The Revlimid® and Dexamethasone doses will be determined by the doses given during the induction phase. Patients will take Revlimid® by mouth daily for 21 days followed by a 7 days of rest and Dexamethasone by mouth on Days 1-4 of each 28 day cycle. Patients will take an aspirin (81 mg) by mouth daily for 28 days. Patients will receive maintenance therapy until their disease gets worse or they have bad effects.

Procedures and testing for all treatment cycles: - Patients will need a blood test (approximately 3 tablespoons). For Cycle 1 only these tests will be done weekly for four weeks and then before treatment cycle. If the patient is having side effects, their blood might be tested more often. - Pregnancy testing for females of child bearing potential. - Patients' side effects will be recorded and they will also have some of the same tests that they had during screening including a physical exam, information about the medications that they are taking will be collected and their ability to do daily activities will be rated. - Patients will be asked to keep a medication and side effect diary and bring it to each clinic visit. - Patients will need to bring all of their Revlimid® medication bottles with them to each visit including bottles that are empty, partly filled or full. - A bone marrow aspiration and biopsy and/or skeletal survey may be completed if their doctor feels it is necessary.

The dose of Revlimid®, Doxil® and/or dexamethasone may be adjusted based on the side effects that may be experienced.

End of Study:

After patients have completed the treatment and maintenance cycles of this study, they will be followed every 3 months to see how they are doing. Patients may be contacted by phone by the study staff if they do not have a regular clinic visit scheduled.

Intervention(s) in this Clinical Trial

• Drug: Lenalidomide, Pegylated Liposomal Doxorubicin, Dexamethasone
  • The Dd combination regimen will be administered every 28 days as follows: Doxil® (D) 40 mg/m² IVPB Day 1 Dexamethasone (d) 40 mg PO daily on Days 1-4 Oral Lenalidomide (R) will be administered in combination with Dd every 28 days as follows: 25 mg QD PO daily on Days 1-21 followed by 7 days rest All subjects will also receive concommitant amoxicillin 250 mg PO BID (or if allergic receive Ciprofloxacin 250 mg BID), acyclovir 400 mg BID or Valacyclovir 500 mg VID, and aspirin 81 mg PO daily until Dd-R chemotherapy is completed. Aspirin will continue after the chemotherapy portion of the study is complete through maintenance therapy. For patients who cannot tolerate aspirin, low molecular weight heparin or therapeutic doses of coumadin may be used in place of aspirin.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Induction Phase

Primary Measures

• Response rate (CR, NCR, PR and MR) to induction Dd-R as assessed using Modified SWOG Response Definitions, and Quality of response (% CR+NCR) to induction Dd-R as assessed using Modified SWOG Response Definitions.
  • Time Frame: 24 months
    Safety Issue?: Yes

Secondary Measures

• Progression Free/Overall Survival, and Tolerability of full dose Revlimid® with full dose Doxil® in combination with reduced schedule dexamethasone assessed during Cycle 1 and at the start of Cycle 2 using, whenever possible, the NCI CTCAE v3.0.
  • Time Frame: 24 months
    Safety Issue?: Yes

Inclusion Criteria:

• Signed informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Diagnosed with active multiple myeloma and be considered to have active disease.
• Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g excreted in a 24-hour urine collection sample).
• ECOG Performance Status of 0-2.
• Performance status of 3 will be allowed if related to bony disease.
• Prior steroid therapy for up to 4 weeks will not exclude the patient from entering the study.
• Bilirubin < 3.0
• Liver enzymes (ALT or AST) < 3 x ULN.
• Must have adequate bone marrow function:
• Absolute neutrophil count > 1,000 cells/mm3 (1.0 x 109/L). Patients with bone marrow
• >50% plasma cells are permitted to have a neutrophil count of < 1,000 cells/mm³.
• Platelets ≥ 50,000 cells/mm³. Patients with bone marrow >50% plasma cells are permitted to have a Platelet count < 50, 000 cells/mm³
• Hemoglobin > 8 g/dL (transfusion allowed to increase the Hgb)
• Must have adequate renal function: Creatinine ≤ 2.5 mg/dL.
• Must have a 2-d echocardiogram indicating LVEF ≥ 50% within 42 days prior to first dose of study drug.
• Able to tolerate aspirin, low molecular weight heparin or coumadin.
• Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control AT THE SAME TIME, at least 4 weeks before taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.

Exclusion Criteria:

• Ongoing severe infection requiring intravenous antibiotic treatment.
• Life expectancy of <3 months.
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 5 years. Concurrent prostate cancer for which the patient is receiving therapy will not be considered an exclusion if the PSA has been stable for three years.
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Patients receiving therapeutic dosages of steroids (dexamethasone 160mg per pulse > 4 pulses) for multiple myeloma.
• Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
• Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Prior chemotherapy for multiple myeloma, except for radiation to symptomatic bony disease, plasmapheresis for hyperviscosity, kyphoplasty and/or vertebroplasty.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Overall Clinical Trial Officials and Contacts

Mohamad Hussein, M.D. Principal Investigator H. Lee Moffitt Cancer Center and Research Institute  

Overall Contact: Mohamad Hussein, M.D. 813-745-8090 mohamad.hussein@moffitt.org

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00617591

Study ID Number: MCC-14986

ClinicalTrials.gov Identifier: NCT00617591

Health Authority: United States: Institutional Review Board

Moffitt Cancer Center Clinical Trials website