Study of Blinatumomab in Richter Transformation

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Brief Title

Study of Blinatumomab in Richter Transformation

Official Title

A Phase II Study of Blinatumomab in Richter Transformation

Brief 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.
    

Detailed Description

      Study Drug Administration:

      The study has 2 study cycles. Cycle 1 is 8 weeks, followed by a 4-8 week break, and then
      Cycle 2 is 4 weeks.

      If you are found to be eligible to take part in this study, you will receive blinatumomab by
      a central venous catheter (CVC) continuously (non-stop) for 1-2 cycles, depending on how you
      are responding to the study drug. A CVC is a sterile flexible tube that will be placed into a
      large vein while you are under local anesthesia. Your doctor will explain this to you in more
      detail, and you will be required to sign a separate consent form for this procedure.

      During Cycle 1, the blinatumomab infusion will be started in the hospital. You will be in the
      hospital for up to at least 16 nights/17 days so that you can be checked for side effects.
      During Cycle 2, the blinatumomab infusion will also be started in the hospital. You will be
      in the hospital for at least 2 nights/3 days. Your doctor will decide when you can leave the
      hospital. Also, if treatment is interrupted for more than 4 hours, for any reason, you will
      need to be admitted to the hospital to restart the treatment.

      Blinatumomab will be delivered by a small pump, which you will carry with you for the whole
      time you receive the drug. You will be given a shoulder or belt bag to hold the pump and
      infusion bag. You will be able to wear regular clothes, walk around, and perform daily living
      activities. You will be given instructions for taking a shower and other activities. There
      will be some things that you should not do, such as go swimming. The study staff will give
      you more information on activities you should not do while receiving the drug.

      You will need to come to MD Anderson to have the infusion bags changed every 48 hours. The
      study staff will let you know when you need to return to the clinic.

      You will be given standard drugs, such as dexamethasone, to help decrease the risk of side
      effects. You may ask the study staff for information about how the drugs are given and their
      risks.

      If you have severe side effects, your study doctor may decide to stop treatment permanently
      or temporarily. If you recover or if the symptoms have improved, the treatment may be
      continued. If the doctor thinks it is needed, you will have an MRI and possibly also a spinal
      tap (lumbar puncture) to test the fluid around the brain, before you restart treatment.

      Length of Study:

      You may receive blinatumomab for up to 2 cycles. You will no longer be able to take the study
      drug if the disease gets worse, if serious side effects occur, or if you are unable to follow
      study directions. Additionally, if your doctor feels it is in your best interests to receive
      an alternative treatment for your Richter Transformation, such as allogeneic stem cell
      transplantation, you will no longer be able to receive blinatumomab.

      Your participation on this study will be over after you have completed follow-up.

      Study Visits:

      At any time the doctor thinks it is needed, you may have a neurological exam.

      Based on the results of the below tests after Cycle 1, the study doctor will decide if you
      will continue to receive the study drug during Cycle 2. If you do not receive the drug during
      Cycle 2, you will have an end-of-study visit (described below).

      On Days 1-17 of Cycle 1 (the time you are in the hospital), every week during Cycle 1, Days
      1-3 of Cycle 2, and every week of Cycle 2:

        -  You will have a physical exam.

        -  Blood (about 2-3 teaspoons) will be drawn for routine tests.

      About 2-4 weeks after Cycles 1 and 2:

        -  You will have a physical exam.

        -  Blood (about 2-3 teaspoons) will be drawn for routine tests.

        -  You will have a bone marrow biopsy/aspiration to check the status of the disease.

        -  You will have a PET/CT or CT scan.

      About 24 weeks after the first dose of study drug and then every 12 weeks after that for up
      to 96 weeks:

        -  You will have a physical exam.

        -  Blood (about 2-3 teaspoons) will be drawn for routine tests.

        -  You will have a PET/CT or CT scan to check the status of the disease.

      End-of-Study Visit:

      After the last dose of study drug, you will continue to receive routine medical care as part
      of your standard care. However, if the disease comes back or worsens while you are receiving
      the study drug:

        -  You will have a physical exam.

        -  Blood (about 2-3 teaspoons) will be drawn for routine tests.

        -  You will have a bone marrow biopsy/aspiration

        -  You will have a PET/CT scan to check the status of the disease.

        -  If the doctor thinks it is needed, you may have a lymph node biopsy to confirm that the
           disease has come back.

        -  If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a
           pregnancy test.

      Long-Term Follow-up:

      After you have completed your participation in this study, you will be asked to participate
      in a separate leukemia department protocol (DR09-0223). The purpose of this protocol is to
      determine how long patients live after receiving leukemia treatment. On this study, if you
      are not having follow-up at MD Anderson, study staff will contact you via phone, email, or
      MyMDAnderson every 6-12 months, to see how you are doing. Phone calls will take approximately
      5-10 minutes. If you agree, you will sign a separate consent form for this study.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate (ORR) in Richter's transformation (RT) After Initial Induction with Blinatumomab Treatment

Secondary Outcome

 Toxicity of Blinatumomab in Richter's Transformation (RT)

Condition

Hematopoietic/Lymphoid Cancer

Intervention

Blinatumomab

Study Arms / Comparison Groups

 Blinatumomab
Description:  Induction phase consists of a single cycle of Blinatumomab therapy. Blinatumomab initiated at 9 mcg/day from day 1-7, followed by 28 mcg/day from day 8-14 (week 2). This is followed by 112 mcg/day from day 15-56. The induction cycle is 8 weeks in duration.
Patients who achieve an objective response after induction are eligible to receive one further cycle of Blinatumomab consolidation, delivered at 112 mcg/day by continuous vein infusion from day 1-28 (total of 4 weeks). Consolidation may be initiated 4-8 weeks after completion of the induction infusion of Blinatumomab.
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

June 22, 2017

Completion Date

February 11, 2022

Primary Completion Date

February 11, 2022

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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Philip A. Thompson, MBBS, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03121534

Organization ID

2016-0765


Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 Amgen

Study Sponsor

Philip A. Thompson, MBBS, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

March 2022