A Study for Patients That Have Been Previously Been Treated in Waldenstrom's Macroglobulinemia or Multiple Myeloma
Condition: Waldenstrom's Macroglobulinemia; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Waldenstrom Macroglobulinemia
Intervention: Enzastaurin
Intervention description: Enzastaurin: Cycle 1 Day 1 only: 3, 125-milligrams (mg) tablets three times on Day 1 (Day 1 total dose = 1125 mg)
Day 2 onwards and subsequent Cycles: 2, 125-mg tablets orally twice a day (500 mg total per day).
Cycle length (all cycles): 28 days. Patients may stay on drug past 8 cycles, (until the study is closed) or until disease progression.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Waldenstrom's Macroglobulinemia; Multiple Myeloma

Summary:

      To determine whether further study of single-agent enzastaurin is warranted in patients with
      previously treated Waldenstrom's Macroglobulinemia or Multiple Myeloma based on response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age.

          -  Patients must have Waldenstrom's Macroglobulinemia (WM) or Multiple Myeloma (MM)
             previously treated with at least 1 and no more than 5 prior therapies.

          -  Treatment with prior autologous transplant is permitted. If a transplant is used as
             consolidation following chemotherapy, without intervening disease progression, it will
             be considered 1 line of treatment with the preceding chemotherapy.

          -  Patients with MM must have a monoclonal protein in the serum of greater than or equal
             to 1 gram per deciliter (g/dL) or monoclonal light chain in the urine protein
             electrophoresis of greater than or equal to 200 milligrams (mg)/ 24 hours, or
             measurable plasmacytoma.

          -  Patients with WM must have an immunoglobulin M (IgM) paraprotein with a minimum IgM
             level of > 2 times the upper limit of normal (ULN), have detectable lymphoplasmacytic
             (LPL) cells in the bone marrow, and be symptomatic for WM.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.

          -  The following laboratory values obtained prior to registration:

               -  Absolute neutrophil count (ANC) greater than or equal to 1000/microliter

               -  Platelet (PLT) count greater than or equal to 75,000/microliter

               -  Total bilirubin less than or equal to 1.5 x ULN (if total is elevated check
                  direct and, if normal, patient is eligible)

               -  Aspartate transaminase (AST) less than or equal to 3 x ULN

               -  Creatinine less than or equal to 1.5 x ULN

               -  Hemoglobin (Hgb) greater than or equal to 8.0 g/dL.

          -  Expected survival of greater than 12 weeks.

          -  The ability to provide informed consent.

          -  Male and female patients with reproductive potential must use an approved
             contraceptive method, if appropriate (for example, intrauterine device [IUD], birth
             control pills, or barrier device) during and for 3 months after discontinuation of
             study treatment. Women with childbearing potential must have a negative serum
             pregnancy test less than or equal to 3 days prior to study enrollment

        Exclusion Criteria:

          -  Prior allogeneic hematopoietic stem cell transplant.

          -  Are unable to discontinue use of non-Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs),
             for example carbamazepine, phenobarbital, and phenytoin. Patients on anti-coagulant
             therapy should be monitored. Ongoing treatment with therapeutic doses of Coumadin is
             prohibited. However, prophylactic, low dose (less than or equal to 2 mg daily)
             Coumadin for deep venous thrombosis (DVT) is allowed. In such cases, prothrombin time/
             international normalized ratio (PT/INR) should be closely monitored.

          -  Have electrocardiogram (ECG) abnormalities including baseline 12-lead ECG with QTc
             interval of greater than 450 milliseconds (msec) in males or greater than 470 msec in
             females, or QRS duration of greater than 100 msec. Patients who have a congenital
             long-QT-syndrome in their own or family medical history should be excluded at the
             investigator's discretion.

          -  Have an uncontrolled infection.

          -  Have prior treatment with Carmustine (BCNU) 6 weeks, alkylating agent 4 weeks, or
             other cytotoxic chemotherapy agents 4 weeks prior to registration in this trial. Have
             prior treatment with biologic therapy less than or equal to 12 weeks or
             corticosteroids less than or equal to 2 weeks prior to registration in this trial.
             However, treatment with less than or equal to 10 mg of prednisone as a chronic therapy
             is allowed.

          -  Have radiation therapy less than or equal to 2 weeks prior to treatment in this trial.

          -  Are pregnant or breast-feeding.

          -  Are being treated with concurrent chemotherapy, immunotherapy, radiotherapy, or any
             ancillary therapy considered investigational.

          -  Are known to be human immunodeficiency virus (HIV) positive.

          -  Were previously treated with enzastaurin.

          -  Patients who are unable to swallow tablets.

          -  Have received treatment within the last 30 days with a drug that has not received
             regulatory approval for any indication at the time of study entry.

          -  Concurrent malignancy that could complicate interpretation of response or safety
             evaluation. Non-melanoma skin cancer and carcinoma in situ of the cervix are not
             exclusions.