Bendamustine Hydrochloride in Treating Patients With Recurrent or Progressive Anaplastic Glioma
Condition: Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm
MeSH terms: Glioblastoma; Astrocytoma; Gliosarcoma; Oligodendroglioma; Brain Neoplasms; Recurrence
Intervention: Bendamustine Hydrochloride; Quality-of-Life Assessment
Intervention description: Given IV; Ancillary studies
Intervention MeSH terms: Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well bendamustine hydrochloride works in treating patients
      with anaplastic glioma or glioblastoma that has come back (recurrent) or growing, spreading
      or getting worse (progressive). Drugs used in chemotherapy, such as bendamustine
      hydrochloride, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have had prior pathologic confirmation of tumor histology,
             anaplastic glioma (AG) or glioblastoma (GBM) and have supratentorial gliomas

          -  Patients must have shown unequivocal evidence for tumor recurrence or progression by
             magnetic resonance imaging (MRI) or computed tomography (CT) scan with contrast

          -  The recurrence to be treated needs to be the 1st or 2nd recurrence of the AG or GBM

          -  If a patient has had surgery prior to enrolling on study, an enhanced MRI or CT scan
             should be done within 96 hours prior to surgery or at least 4-6 weeks after surgery

          -  Patients having undergone recent resection of recurrent or progressive tumor will be
             eligible as long as all of the following conditions apply:

               -  They are > 2 weeks from surgery

               -  They have recovered from the effects of surgery

               -  Evaluable or measurable disease following resection of recurrent tumor is
                  mandated for eligibility into the study

               -  To best assess the extent of residual disease post-operatively, an enhanced
                  CT/MRI should be done no later than 96 hours after surgery or it will need to be
                  done 4-6 weeks post-operatively; if the 96 hour scan is more than 2 weeks from
                  registration, the scan needs to be repeated

          -  A baseline scan should be performed within 14 days prior to registration and on a
             steroid dosage that has been stable for at least 5 days otherwise a new baseline MR/CT
             is required; the same type of scan, i.e., MRI or CT must be used throughout the period
             of protocol treatment for tumor measurement

          -  Patients must have failed prior external beam radiation therapy; a positron emission
             tomography (PET) or thallium single photon emission computed tomography (SPECT), MR
             spectroscopy and MR perfusion, or surgical documentation may be done at the discretion
             of the treating physician if there is a question of radiation changes/necrosis versus
             progressive disease

          -  Stereotactic radiosurgery (SRS):

               -  Patients must have confirmation of true progressive disease rather than radiation
                  necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR
                  perfusion or surgical documentation of disease

               -  At least 12 weeks between completion of SRS and initiation of bendamustine

          -  Interstitial brachytherapy: patients must have confirmation of true progressive
             disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR
             spectroscopy and MR perfusion or surgical documentation of disease

          -  Patients must have had at least one prior chemotherapy regimen that included
             temozolomide and no more than one prior salvage chemotherapy

          -  Patients must have recovered from the toxic effects of prior therapy: 4 weeks from
             prior cytotoxic therapy and/or at least 2 weeks from vincristine, 6 weeks from
             nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic
             agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.
             (radiosensitizer does not count), 4 weeks for experimental biologic agents (epidermal
             growth factor receptor [EGFR] inhibitors, etc) and 7 weeks from Gliadel implantation

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study; patients must sign an authorization for the
             release of their protected health information

          -  Patients must have a life expectancy > 11 weeks

          -  Patients must have a Karnofsky performance status of > 60

          -  White blood cells (WBC) >= 3,000/ul

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 80,000/mm^3

          -  Hemoglobin >= 9 mg/dl (NOTE: eligibility level for hemoglobin may be reached by
             transfusion)

          -  Absolute lymphocyte count >= 200/mm^3

          -  Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase
             (SGPT) < 3 times upper limit of normal (ULN)

          -  Bilirubin < 1.5 times ULN

          -  Serum creatinine < 1.5 mg/dL

          -  Calculated creatinine, glomerular filtration rate (GFR) >= 30 cc/minute

        Exclusion Criteria:

          -  Patients must not have any significant medical illnesses that in the investigator's
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient's ability to tolerate this therapy

          -  Known human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy are excluded from the study

          -  Patients with a history of any other cancer (except non-melanoma skin cancer or
             carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
             for that disease for a minimum of 3 years are ineligible

          -  Patients must not be pregnant or breast feeding and must practice adequate
             contraception

          -  Patients can only be on non-enzyme inducing anti-convulsants; if they are on an enzyme
             inducing anti-convulsant, they may be converted to a non-enzyme inducing
             anticonvulsants

          -  Patients cannot be taking any cytochrome P450, cytochrome P450, family 1, subfamily A,
             polypeptide 2 (CYP1A2) pathway inhibiting or inducing agents (except proton pump
             inhibitors which are allowed) including cimetidine, antidepressants, antibiotics and
             all others

          -  Known sensitivity to bendamustine

          -  Known sensitivity to mannitol