Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: carfilzomib; Dexamethasone; Clarithromycin; Lenalidomide; Dexamethasone; Lenalidomide
Intervention description: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles.; 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib.; 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Intervention MeSH terms: Clarithromycin; Dexamethasone; Dexamethasone acetate; Lenalidomide; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      The purpose of this study is to evaluate the safety and effectiveness of an investigational
      new drug called carfilzomib, in combination with dexamethasone in subjects with newly
      diagnosed multiple myeloma followed by treatment with a combination of drugs clarithromycin
      (Biaxin®), lenalidomide (Revlimid®) and dexamethasone (Decadron®) [BiRD] then lenalidomide
      alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must voluntarily sign and understand written informed consent.

          -  Subject is ≥ 18 years at the time of signing the consent form.

          -  Subject has histologically confirmed multiple myeloma that has never before been
             treated.

          -  Subject had 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 have
             received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid)
             as routine care, or radiation therapy as palliation for pain and/or spinal cord
             compression.

          -  Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, > 10
             mg/dL involved serum free light chain (either kappa or lambda) provided that the serum
             free light chain ratio is abnormal, > 0.2 g/24 hrs urinary M-protein excretion, and/or
             measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either
             CT scanning or MRI.

          -  Subject has a Karnofsky performance status ≥ 60% (> 50% if due to bony involvement of
             myeloma (see Appendix VI).

          -  Subject is able to take prophylactic anticoagulation as detailed in section 9.1
             (patients intolerant to aspirin may use warfarin or low molecular weight heparin).

          -  Subject is registered into the mandatory RevAssist® program, and is willing and able
             to comply with the requirements of RevAssist® program.

          -  If subject is a female of childbearing potential (FCBP),† she must have a negative
             serum or urine pregnancy test with a sensitivity of at least 25 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, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 28
             days 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.

          -  Subjects must meet the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)

               -  Hemoglobin ≥ 7 g/dL

               -  Platelet count ≥ 30,000/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:

          -  Subject has immeasurable MM (no measurable monoclonal protein, free light chains in
             blood or urine, or measureable plasmacytoma on radiologic scanning).

          -  Subject has a prior history of other malignancies unless disease free for ≥ 5 years,
             except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the
             cervix or breast, or localized prostate cancer with Gleason score < 7 with stable
             prostate specific antigen (PSA) levels.

          -  Subject has had myocardial infarction within 6 months prior to enrollment , or
             NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction <
             35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias,
             electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities.

          -  Female subject who is pregnant or lactating.

          -  Subject has known HIV infection

          -  Subject has known active hepatitis B or hepatitis C infection.

          -  Subject has active viral or bacterial infections or any coexisting medical problem
             that would significantly increase the risks of this treatment program.

          -  Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide,
             thalidomide, allopurinol, or carfilzomib.

          -  Subject has a history of thromboembolic event within the past 4 weeks prior to
             enrollment.

          -  Subject has any clinically significant medical or psychiatric disease or condition
             that, in the Investigator's opinion, may interfere with protocol adherence or a
             subject's ability to give informed consent.