A phase II study of blinatumomab in Richter Transformation
Philip A. Thompson
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.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: Blinatumomab
Treatment Location: Only at MDACC
Primary endpoint: · Determine the overall response rate (complete remission plus partial remission) in Richter’s transformation (RT) after initial induction with blinatumomab treatment. Secondary objectives: · Determine the proportion of patients who achieve at least partial remission in induction who subsequently receive a course of consolidation therapy. The primary purposes of this analysis is to determine the feasibility and safety of delivery of >1 cycle of therapy in patients who are responding to treatment. Patients who receive an allogeneic stem cell transplant (alloSCT) after induction will be censored for this analysis. · Assess the safety and feasibility of administering blinatumomab to patients with CLL and Richter’s transformation. · Determine the complete remission rate for RT after induction and consolidation therapy with blinatumomab. · Determine the progression-free survival rate for RT at 1 year after blinatumomab treatment. · Determine the overall survival rate for RT at 1 year after blinatumomab treatment. · Determine the proportion of patients who proceed to allogeneic stem cell transplantation as next treatment after blinatumomab. Exploratory objectives: · Determine pre-treatment immunologic parameters predictive of response to blinatumomab treatment and evaluate treatment-induced immunologic changes in blood and tumor tissue during treatment and correlate with response. · Determine whether specific genomic profiles in transformed cells are predictive of response. · Correlate tumor CD19 expression with response. · Determine the efficacy of blinatumomab in achieving ORR (CR + PR) and MRD-negativity in CLL (CLL will co-exist with RT) in bone marrow by 4-color flow cytometry.
IRB Review and Approval Date: 06/22/2017
Recruitment Status: Open
Projected Accrual: N/A
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.
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.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
Philip A. Thompson
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