Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation

NCT03121534 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2016-0765
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic/Lymphoid Cancer; Richter's Transformation

Keywords

Hematopoietic/Lymphoid Cancer; Richter's transformation; RT; Blinatumomab; Dexamethasone; Decadron

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Response

  Response is defined as complete remission (CR) plus partial remission (PR). Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules. Partial Remission (PR) is any two of the following must decrease \>/= 50% from baseline: lymph nodes, Liver and/or spleen size, circulating lymphocyte count in addition to one of the following: platelets \>/= 100 x 10\^9/L or \>/= 50% increase from baseline, Hemoglobin \>/= 11.0 g/dL or \>/= 50% increase from baseline or marrow presence of CLL cells, or of B-lymphoid nodules, or not done.

  2 months

Secondary Outcomes (3)

• Number of Participants to Achieve Complete Remission

  Up to 4 years, 8 months

• Progression Free Survival

  Up to 4 years, 8 months

• Overall Survival

  Up to 4 years, 8 Months

Study Arms (1)

Ibrutinib, Nivolumab and Blinatumomab

EXPERIMENTAL

2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab. Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. 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. blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.

Drug: Blinatumomab; Drug: Dexamethasone; Drug: Ibrutinib; Drug: Nivolumab

Interventions

Blinatumomab DRUG

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.

Also known as: BLINCYTO®

Ibrutinib, Nivolumab and Blinatumomab

Dexamethasone DRUG

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.

Also known as: Decadron

Ibrutinib, Nivolumab and Blinatumomab

Ibrutinib DRUG

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.

Also known as: Imbruvica™

Ibrutinib, Nivolumab and Blinatumomab

Nivolumab DRUG

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.

Also known as: Opdivo

Ibrutinib, Nivolumab and Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Co-operative Oncology Group (ECOG) performance status \< or =2.
• Age \> or =18 years at the time of informed consent.
• Able to provide informed consent and be willing to participate in study schedule and events.

You may not qualify if:

• Other active malignancy receiving systemic therapy.
• 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.
• Known active DLBCL in the CNS (confirmed by CSF analysis).
• Current autoimmune disease requiring \>/= 20mg/day of prednisone or systemic immunosuppressive therapy (eg. with cyclosporine or azathioprine).
• Allogeneic HSCT within 24 weeks before the start of protocol-specified therapy.
• 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.
• 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.
• Radiotherapy within 2 weeks before the start of protocol-specified therapy.
• 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).
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive).
• Patient is pregnant or breast feeding.
• 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.
• 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.
• 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.
• Currently receiving treatment in another investigational device or drug study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Amgen: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Thompson PA, Jiang X, Banerjee P, Basar R, Garg N, Chen K, Kaplan M, Nandivada V, Cortes AKN, Ferrajoli A, Keating MJ, Peterson CB, Andreeff M, Rezvani K, Wierda WG. A phase two study of high dose blinatumomab in Richter's syndrome. Leukemia. 2022 Sep;36(9):2228-2232. doi: 10.1038/s41375-022-01649-3. Epub 2022 Aug 8.

  PMID: 35941212 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

blinatumomab; Dexamethasone; Calcium Dobesilate; ibrutinib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Philip Thompson MD.
• Organization: The University of Texas MD Anderson Cancer Center

PAThompson2@mdanderson.org

713-745-5732

Study Officials

• Philip A. Thompson, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: April 20, 2017
• Study Start: June 22, 2017
• Primary Completion: February 11, 2022
• Study Completion: February 11, 2022
• Last Updated: February 17, 2023
• Results First Posted: February 17, 2023

Record last verified: 2023-01

Locations

US (1)