Phase II Study of Thalidomide, Clarithromycin, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: thalomid; lenalidomide; clarithromycin; dexamethasone
Intervention description: Cycles 1-4
• Thalidomide (50mg daily for days 1-7, thereafter 100mg daily for days 8-28 of the first 28 day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 for each subsequent cycle); During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation)
• Lenalidomide (25 mg daily days 1-21 of every 28 day cycle)
During BiRD phase • 25mg daily days 1-21 of every 28 day cycle)
During Maintenance Phase
• 25 mg daily for days 1-21 out of a 28 day cycle; During T-BiRD Phase • Clarithromycin (500mg twice daily for each 28 day cycle)
During BiRD Phase:
• Clarithromycin (500mg twice daily for each 28 day cycle); During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation)
• Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)
During BiRD Phase:
• Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)
During Maintenance Phase
• Dexamethasone 20 mg weekly (days 1,8, 15, 22 out of a 28 day cycle)
Intervention MeSH terms: Clarithromycin; Thalidomide; Dexamethasone; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myeloma; newly diagnosed multiple myeloma

Summary:

      Study Objectives

        1. Evaluate the efficacy of the combination of thalidomide (Thalomid®), clarithromycin
           (Biaxin®), lenalidomide (Revlimid®), and dexamethasone (Decadron®) as an induction
           therapy for patients with newly diagnosed multiple myeloma (MM).

        2. Evaluate the efficacy of the addition of thalidomide (Thalomid®) to BiRD combination
           therapy as a therapy to increase the complete response rate for patients with newly
           diagnosed multiple myeloma.

        3. Evaluate the safety of the combination of clarithromycin, lenalidomide, dexamethasone,
           and thalidomide as a therapy for patients with newly diagnosed MM
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must voluntarily sign and understand written informed consent.

          -  Age > 18 years at the time of signing the consent form.

          -  Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be
             eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell
             proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).

          -  Newly diagnosed myeloma.

          -  No anti-myeloma therapy within 14 days prior to initiation of study treatment except
             for corticosteroids with a maximum allowed dosage equivalent to three pulses of
             dexamethasone (40mg daily for 4 days equals one pulse). Patients may be receiving
             adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine
             care.

          -  Measurable disease as defined by > 1.0 g/dL serum monoclonal protein, >0.1 g/dL serum
             free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable
             plasmacytoma(s).

          -  Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma.

          -  Able to take aspirin daily as prophylactic anticoagulation. (patients intolerant to
             ASA may use warfarin or low molecular weight heparin)

          -  All study participants must be registered into the mandatory RevAssist® and
             S.T.E.P.S.® programs, and be willing and able to comply with the requirements of
             RevAssist® and the S.T.E.P.S.® programs.

          -  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 and thalidomide (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, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 4
             weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
             testing. Men must agree to use a latex condom during sexual contact with females of
             child bearing potential even if they have had a successful vasectomy.

          -  Life expectancy ≥ 3 months

          -  Subjects must meet the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)

               -  Platelets count ≥ 75,000/mm3 (75 x 109/L)

               -  Serum SGOT/AST <3.0 x upper limits of normal (ULN)

               -  Serum SGPT/ALT <3.0 x upper limits of normal (ULN)

               -  Serum creatinine <2.5 mg/dL (221 µmol/L)

               -  Serum total bilirubin <2.0 mg/dL (34 µmol/L)

        Exclusion Criteria:

          -  Patients with non-secretory MM (no measurable monoclonal protein, free light chains,
             and/or M-spike in blood or urine).

          -  Prior history of other malignancies (except for basal cell or squamous cell carcinoma
             of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5
             years.

          -  Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital
             Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities.

          -  Pregnant or lactating females are ineligible.

          -  Given the potential of the study drugs to trigger or worsen HIV viremia and the
             incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or
             HIV-2 positive patients will be excluded. The interactions of HAART with study drugs
             have not been determined.

          -  Active hepatitis B or hepatitis C infection.

          -  Active viral or bacterial infections or any coexisting medical problem that would
             significantly increase the risks of this treatment program.

          -  Any coexisting medical problem or laboratory evaluation that, in the treating
             physician's or principal investigator's opinion, makes the patient unsuitable to
             participate in this clinical trial.

          -  Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.

          -  History of thromboembolic event within the past 6 months prior to enrollment.