Velcade + Cyclophosphamide in Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Velcade; Cyclophosphamide; Revlimid
Intervention description: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. Patients who cannot tolerate SC VELCADE will be converted to the same dose, given intravenously (IV), per discretion of the treating physician.; Cyclophosphamide: 300 mg/m2, given orally on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Patients who cannot swallow cyclophosphamide pills will be converted to the same dose, given intravenously (IV).; Lenalidomide (odd cycles [9,11,13, etc.]: 10 mg, given orally on days 1-21. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. On even cycles, patients will be prescribed enough lenalidomide to take at home, as instructed, for one cycle. This will be prescribed through the mandatory RevlimidREMS® program. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up.
Patients who take more than the prescribed dose of lenalidomide should be instructed to seek emergency medical care if needed and contact study staff immediately.
Intervention MeSH terms: Cyclophosphamide; Lenalidomide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to estimate the overall response rate (ORR), defined as
      partial response (PR) or better at any time during induction therapy. The success of the
      therapy will be determined by ORR with strong consideration given to the secondary endpoints
      of tolerability, duration of response, and quality of life (QOL).

      All patients will be treated with the same experimental regimen. Several novel features are
      being explored: the substitution of cyclophosphamide for melphalan; once weekly AND
      subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating
      bortezomib and lenalidomide in maintenance.

      The investigators hypothesize that this regimen will prove to be tolerable and effective in
      inducing and maintaining remission in a patient population that is historically very
      difficult to treat, namely Multiple Myeloma (MM) patients who are too elderly or suffer
      comorbidities, such as renal insufficiency, that otherwise complicate aggressive therapies
      like autologous stem-cell transplantation (ASCT). In short, the investigators view this as
      the "Multiple Myeloma trial for non-trial candidates."
    

Eligibility criteria:

        Inclusion Criteria:

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

          -  Age ≥18 years at the time of signing the informed consent form.

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Multiple Myeloma (MM) diagnosed according to the following standard criteria (all
             three criteria must be met):

               -  Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven
                  plasmacytoma

               -  Laboratory tests meet the levels specified in the protocol

          -  Measurable disease requiring systemic therapy.

          -  No prior systemic therapy or radiation therapy active against myeloma lasting more
             than four weeks duration. Any prior therapy must be completed a minimum of 21 days
             before starting study drugs. Enrollment of subjects who require radiotherapy (which
             must be localized in its field size) should be deferred until the radiotherapy is
             completed and 3 weeks have elapsed since the last date of therapy.

          -  Karnofsky performance status (KPS) of ≥ 60% at study entry.

          -  In order to obtain lenalidomide, patients must be registered into the mandatory
             RevlimidREMS® program during the maintenance phase of therapy, and be willing and able
             to comply with the requirements of RevlimidREMS®

          -  Female subjects must be postmenopausal for at least 1 year before the screening visit
             or surgically sterilized. If females are of childbearing potential, they must adhere
             to required pregnancy testing; male and female subjects must use specified effective
             birth control methods.

          -  Patients should receive concomitant therapy with bisphosphonates, regardless of the
             presence of bony lesions, although study physicians may use their discretion based on
             presence of renal insufficiency or other mitigating factors.

        Exclusion Criteria:

          -  Abnormal laboratory tests within the ranges specified in the protocol

          -  Serum creatinine will not be used to exclude patients. Patients on renal-replacement
             therapy (e.g., hemodialysis or peritoneal dialysis) will be eligible to participate.

          -  Light-chain (AL) amyloidosis. Patients with secondary amyloidosis due to MM are
             eligible.

          -  ≥ Grade 2 peripheral neuropathy

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any
             Electrocardiography (ECG) abnormality at screening must be documented by the
             investigator as not medically relevant.

          -  Hypersensitivity to VELCADE, boron, mannitol, or any other component of protocol
             therapy.

          -  Female subject is pregnant or lactating. Confirmation that the subject is not pregnant
             must be established by a negative serum beta-human chorionic gonadotropin (b- hCG)
             pregnancy test result obtained during screening as specified in section 7.11.

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period, or a positive urine pregnancy test on Day 1 before first dose of
             study drug, if applicable.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Diagnosed or treated for another malignancy within 2 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial.

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known HIV positivity

          -  Known active hepatitis A, B or C