Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Velcade; Cyclophosphamide; Chloroquine
Intervention MeSH terms: Chloroquine; Cyclophosphamide; Bendamustine Hydrochloride; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myeloma; multiple myeloma; relapsed myeloma; refractory myeloma

Summary:

      This pilot phase II trial studies how well giving bortezomib and cyclophosphamide together
      with chloroquine works in treating patients with relapsed or refractory multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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             not part of normal medical care, with the understanding that consent may be withdrawn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.

          2. Female subject is either post-menopausal for at least 1 year before the screening
             visit, is surgically sterilized or if they are of childbearing potential, agree to
             practice 2 effective methods of contraception from the time of signing the informed
             consent form through 30 days after the last dose of VELCADE, or agree to completely
             abstain from heterosexual intercourse. Male subjects, even if surgically sterilized
             (ie, status postvasectomy) must agree to 1 of the following: practice effective
             barrier contraception during the entire study treatment period and through a minimum
             of 30 days after the last dose of study drug, or completely abstain from heterosexual
             intercourse.

          3. Diagnosis of multiple myeloma based on standard criteria as follows:

             Major Criteria:

             I. Plasmacytomas on tissue biopsy

             II. Bone marrow plasmacytosis (>30% plasma cells)

             III. Monoclonal immunoglobulin spike on serum electrophoresis (IgG >3.5 G/dL or IgA >
             2.0 G/dL) or kappa or lambda light chain excretion> 1 G/day on 24 hour urine protein
             electrophoresis

             Minor Criteria

               1. Bone marrow plasmacytosis (10 to 30% plasma cells)

               2. Monoclonal immunoglobulin present but of lesser magnitude than given under major
                  criteria

               3. Lytic bone lesions

               4. Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

             Any of the following sets of criteria will confirm the diagnosis of Multiple Myeloma:

               -  Any two of the major criteria

               -  Major criterion I plus minor criterion b, c, or d

               -  Major criterion III plus minor criterion a or c

               -  Minor criteria a, b and c or a, b and d

          4. Measurable disease, defined as a monoclonal immunoglobulin spike on serum
             electrophoresis of ≥ 1 Gm/dL and/or urine monoclonal immunoglobulin spike of ≥ 200
             mg/24 hours.

          5. Patients must have refractory myeloma as defined by a greater than 25% increase in
             their M-protein. They should have progressed on a combination of VELCADE and
             cyclophosphamide.

          6. Non-secretors must have measurable protein by Freelite or measurable disease such as
             plasmacytoma to be eligible.

          7. Karnofsky performance status ≥ 50

          8. Patients treated with local radiotherapy with or without a brief exposure to steroids
             are eligible. Patients who require concurrent radiotherapy should have entry to the
             protocol deferred until the radiotherapy is completed

          9. Meets the following pretreatment laboratory criteria at Baseline (Day 1 of Cycle 1,
             before study drug administration)

               -  Absolute neutrophil count ≥ 0.5 x 10^3/uL

               -  Calculated or measured creatinine clearance ≥ 30 mL/min

         10. Age 18 years or older

        Exclusion Criteria:

          1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein (M-protein) and skin changes)

          2. Plasma cell leukemia

          3. Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus
             erythematosis, rheumatoid arthritis

          4. Infection not controlled by antibiotics

          5. HIV infection. Patients should provide consent for HIV testing according to the
             institution's standard practice

          6. Known active hepatitis B or C

          7. Patient had myocardial infarction within 6 months prior to enrollment, New York
             Hospital Association (NYHA) Class III or IV heart failure, (see appendix D),
             uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
             electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities. Prior to study entry, any ECG abnormality at screening must be
             documented by the investigator as not medically relevant.

          8. Diagnosed or treated for another malignancy within 3 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.

          9. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
             require concurrent 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.

         10. Other serious medical or psychiatric illness that could potentially interfere with the
             completion of treatment according to this protocol

         11. Female subject is pregnant or lactating. Confirmation that the subject is not pregnant
             must be established by a negative serum B-human chorionic gonadotropin (B hCG)
             pregnancy test result obtained during screening. Pregnancy testing is not required for
             postmenopausal or surgically sterilized women.

         12. Patient has > Grade 2 peripheral neuropathy

         13. Patient has known hypersensitivity to VELCADE, boron or mannitol, quinidine or
             quinidine derivatives or to cyclophosphamide or any component of the formulation.

         14. 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.

         15. Patients with preexisting retinal or visual field changes.

         16. Patient has > 1.5 x upper limit of normal Total Bilirubin