Clinical trial NCT00719901 (phase 1/phase 2, status: terminated)
Conditions: refractory multiple myeloma, stage i multiple myeloma, stage ii multiple myeloma, stage iii multiple myeloma
ICD codes: D46.4, D46.1, D46.A, D46.0, D46.20, D46.21, D46.22, C90.01, C90.02, C90.00, C90.01, C90.02, C90.00, C90.01, C90.02, C90.00
Drugs: obatoclax mesylate, bortezomib
SMILES: COC1=CC(=N\C1=C/C1=C(C)C=C(C)N1)C1=CC2=CC=CC=C2N1, ClCCN(CCCl)P1(=O)NCCCO1
Reason stopped: 
    this trial was terminated due to slow accrual and the drug supply of obatoclax during the phase
    i; therefore, the phase ii portion will never open.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:

               -  Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or
                  biopsy proven plasmacytoma

               -  Symptomatic disease (e.g.,anemia, hypercalcemia, bone disease, or renal
                  dysfunction) that requires the initiation of therapy

          -  Measurable diseases assessed by one of the following:

               -  Monoclonal plasma cells detectable in the bone marrow

               -  Monoclonal serum spike detectable by serum protein electrophoresis or
                  immunofixation

               -  Monoclonal protein detectable in the urine by electrophoresis or immunofixation

               -  Abnormal levels of the serum free light chains with an abnormal ratio between
                  kappa and lambda

          -  Progressive disease after ≥ 1 prior therapy for myeloma

          -  Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease
             progression during therapy OR completed bortezomib therapy within the past 6 weeks

               -  No prior discontinuation of bortezomib therapy due to drug intolerance

          -  No known brain metastases

          -  No intracranial edema, intracranial metastasis, or active epidural disease

               -  Patients with lytic lesions of the cranium secondary to myeloma are eligible

          -  ECOG performance status 0-2

          -  Life expectancy > 6 months

          -  ANC ≥ 1,000/mm³

          -  Platelet count ≥ 50,000/mm³

          -  Bilirubin normal

          -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

          -  Creatinine ≤ 2 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No peripheral neuropathy > NCI toxicity grade 2

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to obatoclax mesylate or bortezomib

          -  No concurrent uncontrolled illness including, but not limited to the following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia, including QTc > 450 msec

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  No history of seizure disorder

          -  No other neurological disorder or dysfunction that, in the opinion of the
             investigator, would confound the evaluation of neurologic and other adverse events
             associated with obatoclax mesylate

          -  At least 14 days since prior chemotherapy and recovered

          -  More than 28 days since prior experimental drugs and/or investigational agents

          -  No concurrent CYP interactive medications

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent anticancer therapy

               -  Growth factors and bisphosphonates are allowed as medically indicated

               -  Prednisone (≤ 10 mg per day) allowed provided there has been no dose increase
                  within the past 2 weeks

          -  No other concurrent investigational agents