Pegylated Liposomal Doxorubicin, Low Freq Dexamethasone & Revlimid (Dd-R) in Newly Diagnosed Multiple Myeloma (MM)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide; Pegylated Liposomal Doxorubicin (PLD); Dexamethasone
Intervention description: 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
Intervention MeSH terms: Dexamethasone; Doxorubicin; Liposomal doxorubicin; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lenalidomide; Revlimid; Pegylated Liposomal Doxorubicin; Doxil; Dexamethasone; Decadron

Summary:

      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.
    

Eligibility criteria:

        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).

          -  Eastern Cooperative Oncology Group (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: alanine transaminase or aspartate transaminase (ALT or AST) < 3 x upper
             limit of normal (ULN)

          -  Must have adequate bone marrow function:

          -  Absolute neutrophil count > 1,000 cells/mm³ (1.0 x 10^9/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 left ventricular ejection fraction (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 to 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 prostatic specific
             antigen (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