Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation
Condition: Hematopoietic/Lymphoid Cancer; Richter's Transformation
Intervention: Blinatumomab; Dexamethasone; Ibrutinib; Nivolumab
Intervention description: Patients will receive blinatumomab as a continuous IV infusion, commencing on day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week .
blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28. This will be followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days.blinatumomab treatment-free interval.; Dexamethasone 20 mg by mouth or vein 24 hours prior to and within 1 hour before start of treatment in each treatment cycle. If treatment is interrupted for >4 hours at any point, Dexamethasone treatment given before re-initiation of therapy. Dexamethasone 8 mg by mouth or vein every 8 hours given for 48 hours at the commencement of the infusion and after each dose increment.; Ibrutinib treatment will commence on cycle 1, day 1 at 420mg/d. Dose reductions to 280mg/d or 140mg/d are allowed per treating physician discretion, but the reason must be documented in the medical record. Ibrutinib will be given continuously until disease progression or toxicity.; Patients will receive nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
Intervention MeSH terms: Dexamethasone; Nivolumab; Blinatumomab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hematopoietic/Lymphoid Cancer; Richter's transformation; RT; Blinatumomab; Dexamethasone; Decadron

Summary:

      The goal of this clinical research study is to learn if blinatumomab can help to control
      Richter Transformation (RT, a type of blood cancer). The safety of this drug will also be
      studied.

      This is an investigational study. Blinatumomab is FDA approved and commercially available for
      the treatment of acute lymphoblastic leukemia (ALL). It is investigational to use
      blinatumomab to treat patients with RT. The study doctor can explain how the study drug is
      designed to work.

      Up to 21 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with previously treated CLL and biopsy-proven Richter's transformation with
             DLBCL histology according to IWCLL criteria (Richter Transformation - RT) and CD19
             positive by flow cytometry OR immunohistochemistry.

          2. Eastern Co-operative Oncology Group (ECOG) performance status < or =2.

          3. Age > or =18 years at the time of informed consent.

          4. Able to provide informed consent and be willing to participate in study schedule and
             events.

        Exclusion Criteria:

          1. Other active malignancy receiving systemic therapy.

          2. History or presence of clinically relevant disorder affecting the CNS such as
             epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries,
             dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or
             psychosis, with the exception of a history of CNS lymphoma that is controlled with
             intrathecal therapy.

          3. Known active DLBCL in the CNS (confirmed by CSF analysis).

          4. Current autoimmune disease requiring >/= 20mg/day of prednisone or systemic
             immunosuppressive therapy (eg. with cyclosporine or azathioprine).

          5. Allogeneic HSCT within 24 weeks before the start of protocol-specified therapy.

          6. Active Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg
             criteria, active chronic GvHD requiring systemic treatment or requirement for GvHD
             prophylaxis with cyclosporine or tacrolimus.

          7. Cancer chemotherapy within 2 weeks before start of protocol-specified therapy, with
             the exception of intrathecal chemotherapy, dexamethasone, and oral small molecule
             inhibitors such as BTK-inhibitor, PI3K-inhibitor, or Bcl-2-inhibitor, which are
             allowed until the start of protocol-specified therapy). In addition, any subject whose
             organ toxicity (excluding hematologic) from prior treatment has not resolved to no
             more than CTCAE grade 1.

          8. Radiotherapy within 2 weeks before the start of protocol-specified therapy.

          9. Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and/or ALT
             (SGPT) and/or ALP > or =5 x upper limit of normal (ULN); b) Total bilirubin > or = 1.5
             x ULN, unless due to Gilbert's disease; c) Creatinine > or = 2.0 x ULN or creatinine
             clearance <50 mL/min (calculated).

         10. Known infection with human immunodeficiency virus (HIV) or chronic infection with
             hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive).

         11. Patient is pregnant or breast feeding.

         12. Woman of childbearing potential and is not willing to use 2 highly effective methods
             of contraception while receiving protocol-specified therapy and for an additional 24
             hours after the last dose of protocol-specified therapy.

         13. Male who has a female partner of childbearing potential, and is not willing to use 2
             highly effective forms of contraception while receiving protocol-specified therapy and
             for at least an additional 24 hours after the last dose of protocol-specified therapy.

         14. Male who has a pregnant partner, and is not willing to use a condom during sexual
             activity while receiving protocol-specified therapy and for 3 months after the last
             dose of protocol-specified therapy.

         15. Currently receiving treatment in another investigational device or drug study.

         16. Subject previously treated with blinatumomab.

         17. History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the Principal
             Investigator would pose a risk to subject safety or interfere with the study
             evaluation, procedures or completion.