Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Blinatumomab in Richter Transformation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03121534
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : May 20, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.


Condition or disease Intervention/treatment Phase
Hematopoietic/Lymphoid Cancer Richter's Transformation Drug: Blinatumomab Drug: Dexamethasone Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Blinatumomab in Richter Transformation
Actual Study Start Date : June 22, 2017
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 1, 2021


Arm Intervention/treatment
Experimental: Blinatumomab

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.

Drug: Blinatumomab

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.


Drug: Dexamethasone
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.
Other Name: Decadron




Primary Outcome Measures :
  1. Overall Response Rate (ORR) in Richter's transformation (RT) After Initial Induction with Blinatumomab Treatment [ Time Frame: 2 months ]
    ORR defined as complete remission plus partial remission. Response assessed according to revised Cheson criteria.


Secondary Outcome Measures :
  1. Toxicity of Blinatumomab in Richter's Transformation (RT) [ Time Frame: 4 weeks after completion of the consolidation cycle ]
    Toxicity defined as grade 3 or higher cytokine release syndrome or therapy-related neurotoxicity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121534


Contacts
Layout table for location contacts
Contact: Philip A. Thompson, MBBS 713-792-7430 pathompson2@mdanderson.org

Locations
Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Amgen
Investigators
Layout table for investigator information
Principal Investigator: Philip A. Thompson, MBBS M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03121534     History of Changes
Other Study ID Numbers: 2016-0765
First Posted: April 20, 2017    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Hematopoietic/Lymphoid Cancer
Richter's transformation
RT
Blinatumomab
Dexamethasone
Decadron
Additional relevant MeSH terms:
Layout table for MeSH terms
Dexamethasone
Dexamethasone acetate
Blinatumomab
BB 1101
Antibodies, Bispecific
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors