Overview

This trial is active, not recruiting.

Condition leukemia
Treatments rituximab, urelumab
Phase phase 2
Targets CD137, CD20
Sponsor M.D. Anderson Cancer Center
Collaborator Bristol-Myers Squibb
Start date July 2015
End date July 2020
Trial size 24 participants
Trial identifier NCT02420938, 2014-0932, NCI-2015-00805

Summary

The goal of this clinical research study is to learn if urelumab given in combination with rituximab can help to control CLL or SLL. The safety of the drug combination will also be studied.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive Rituximab 375 mg/m2 by vein weekly for the first 4 weeks (Days 1, 8, 15, 22) then the day prior to each subsequent dose of Urelumab for the 12-week course. Urelumab 8 mg by vein given every 3 weeks for 4 doses, starting Day 2 of the course. Urelumab doses administered approximately 24 hours after the Rituximab doses. Up to two 12-week courses of treatment administered (total of maximum 12 doses of Rituximab and 8 doses of Urelumab).
rituximab Rituxan
375 mg/m2 by vein weekly for the first 4 weeks (Days 1, 8, 15, 22) then the day prior to each subsequent dose of Urelumab for the 12-week course.
urelumab
8 mg by vein given every 3 weeks for 4 doses, starting Day 2 of the 12-week course.

Primary Outcomes

Measure
Overall Response (OR) of Urelumab and Rituximab in Participants with High-Risk Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL).
time frame: 12 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Patients will have a diagnosis of CLL or SLL who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL) and are relapsed and/or refractory after at least one prior therapy. 2. Age 18 years or older. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 100 bpm)),congestive heart failure, or myocardial infarction within 2 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. 4. History of stroke or cerebral hemorrhage within 2 months. 5. Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure >/= 160 mmHg or diastolic >/= 100 mmHg). 6. Known evidence of active cerebral/meningeal CLL. Patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration. 7. Known active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring steroid therapy. 8. Patients with autoimmune diseases are excluded: Patients with a history of Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, Wegener's granulomatosis). 9. Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with active acute or chronic graft-versus host disease are excluded. Patients must be off immunosuppression for GVHD for at least 30 days before cycle 1 day 1. 10. Patients with organ allografts (such as renal transplant) are excluded. 11. History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), auto immune, or grade 3-4 drug-related hepatitis). 12. Patients who are on high-dose steroids (doses >10mg/day of prednisone or equivalent) or immune suppression medications. Note: Patients on high-dose steroids (doses >10mg/day of prednisone or equivalent) or immune suppression medications are eligible provided these drugs are discontinued at least 3 days prior to starting on the study drugs. 13. Patients with uncontrolled active infection (viral, bacterial, and fungal) are not eligible. 14. Current or chronic hepatitis B or C infection, or known seropositivity for HIV. Note: Patients with previous history of Hepatitis B (who have cleared the infection and have natural immunity, i.e. Hep B core antibody positive cases) are excluded if prophylaxis against Hep B reactivation with antiviral agents (such as entecavir) is recommended, after consultation with gastroenterologist/hepatologist or infectious disease team. 15. Patient is pregnant or breast-feeding. 16. Concurrent use of investigational therapeutic agent. 17. Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply. 18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study. 19. Patients with Richter's transformation are not allowed in the study.

Additional Information

Official title Urelumab (CD137 mAb) Combined With Rituximab for Relapsed, Refractory or High-risk Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Principal investigator Nitin Jain, MBBS
Description Study Drug Administration: If you are found to be eligible to take part in this study, you will receive rituximab by vein over 4-6 hours on Days 1, 8, 15, 22, 43, and 64 of each 84 day (12 week) cycle. You will receive urelumab by vein over about 1 hour on Days 2, 23, 44, and 65 of each cycle. There will be a 2-week period between each study cycle. Study Visits: On Days 1, 8, 15, 22, 43, and 64 of each cycle: - Blood (about 2 tablespoons) will be drawn for routine tests. - You will have a physical exam. On Days 2, 29, 36, 50, 57, 71, and 78 of each cycle, blood (about 2 tablespoons) will be drawn for routine tests. At the end of each cycle (about Day 85): - Blood (about 2 tablespoons) will be drawn for routine tests. - You will have a physical exam. - You will have a bone marrow aspiration and biopsy to check the status of the disease. - You will have a CT or PET scan to check the status of the disease. You will have blood draws, CT scans (or PET scans) and/or bone marrow aspiration and biopsies at any time that the doctor thinks it is needed while you are on study. Length of Study: You may receive up to 2 cycles of study drugs. However, your study doctor may allow you to receive the study drugs beyond Cycle 2. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. End-of-Study Visit: If you are taken off study for any reason, the following tests and procedures will be performed: - You will have a physical exam. - Blood (about 2-3 tablespoons) will be drawn for routine tests. - If the doctor thinks it is needed, you will have a bone marrow aspirate and CT or PET scan to check the status of the disease. Long-Term Follow-Up: After you are no longer on study, 1 time every month: - You will have a physical exam. - Blood (about 2-3 tablespoons) will be drawn for routine tests. Every 3 months, if the doctor thinks it is needed, you will have a bone marrow aspirate and CT or PET scan to check the status of the disease. Other Testing: The study staff may ask you to take part in other MD Anderson clinical research study (PA13-0291) for additional research testing. The study doctor will discuss this with you and, if you decide to take part, you will sign a separate consent document. This is an investigational study. Urelumab is not FDA approved or commercially available. Rituximab is FDA approved and commercially available for the treatment of patients with CLL. The use of these drugs in combination is investigational. The study doctor can explain how the drugs are designed to work. Up to 24 participants will be enrolled in this study. All will take part at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.
Location data was received from the National Cancer Institute and was last updated in July 2016.