Ignite Creation Date:
2025-12-26 @ 11:08 AM
Ignite Modification Date:
2026-03-20 @ 6:52 AM
Study NCT ID:
NCT02420912
Status:
COMPLETED
Last Update Posted:
2024-03-20
First Post:
2015-04-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Nivolumab Combined With Ibrutinib for Relapsed, Refractory or High-Risk Untreated Patients With Chronic Lymphocytic Leukemia (CLL)
Status:
COMPLETED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well nivolumab and ibrutinib work when given together in treating patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or Richter transformation that has come back after a period of improvement (relapsed), does not respond to treatment (refractory), or is at high risk of spreading and has not been treated. Immunotherapy with monoclonal antibodies, such as niolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving nivolumab together with ibrutinib may kill more cancer cells.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the efficacy (response rate) of nivolumab in combination with ibrutinib in patients with relapsed/refractory or high-risk untreated chronic lymphocytic leukemia (CLL).
II. Determine the response rate (complete response \[CR\]/complete response with incomplete marrow recovery \[CRi\]) by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. (Cohort I) III. Determine the conversion rate from partial response (PR) to CR/CRi by 2008 IWCLL criteria. (Cohort II) IV. Determine the response rate (CR/CRi). (Cohort III)
SECONDARY OBJECTIVES:
I. To determine the safety of nivolumab in combination with ibrutinib in patients with relapsed, refractory or high-risk untreated CLL/Richter transformation (RT).
II. To determine the progression-free survival of patients with relapsed, refractory or high-risk untreated CLL/RT treated with nivolumab in combination with ibrutinib.
III. To determine the overall survival of patients with relapsed, refractory or high-risk untreated CLL/RT treated with nivolumab in combination with ibrutinib.
EXPLORATORY OBJECTIVES:
I. To study immunological and molecular changes in peripheral blood, lymph node, and bone marrow in response to nivolumab and ibrutinib therapy.
OUTLINE: Patients are assigned to 1 of 3 treatment cohorts.
COHORT I (NO CURRENT IBRUTINIB TREATMENT): Patients receive nivolumab intravenously (IV) over 1 hour on days 1 and 15 and ibrutinib orally (PO) once daily (QD) on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
COHORT II (IBRUTINIB TREATMENT \> 9 MONTHS): Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
COHORT III (RICHTER TRANSFORMATION): Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity
\* Note: After 3 cycles of treatment, nivolumab administration may be decreased to once every 4 weeks in all cohorts, in consultation with the study principal investigator.
After completion of study treatment, patients are followed up monthly for 1 year.
I. To determine the efficacy (response rate) of nivolumab in combination with ibrutinib in patients with relapsed/refractory or high-risk untreated chronic lymphocytic leukemia (CLL).
II. Determine the response rate (complete response \[CR\]/complete response with incomplete marrow recovery \[CRi\]) by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. (Cohort I) III. Determine the conversion rate from partial response (PR) to CR/CRi by 2008 IWCLL criteria. (Cohort II) IV. Determine the response rate (CR/CRi). (Cohort III)
SECONDARY OBJECTIVES:
I. To determine the safety of nivolumab in combination with ibrutinib in patients with relapsed, refractory or high-risk untreated CLL/Richter transformation (RT).
II. To determine the progression-free survival of patients with relapsed, refractory or high-risk untreated CLL/RT treated with nivolumab in combination with ibrutinib.
III. To determine the overall survival of patients with relapsed, refractory or high-risk untreated CLL/RT treated with nivolumab in combination with ibrutinib.
EXPLORATORY OBJECTIVES:
I. To study immunological and molecular changes in peripheral blood, lymph node, and bone marrow in response to nivolumab and ibrutinib therapy.
OUTLINE: Patients are assigned to 1 of 3 treatment cohorts.
COHORT I (NO CURRENT IBRUTINIB TREATMENT): Patients receive nivolumab intravenously (IV) over 1 hour on days 1 and 15 and ibrutinib orally (PO) once daily (QD) on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
COHORT II (IBRUTINIB TREATMENT \> 9 MONTHS): Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
COHORT III (RICHTER TRANSFORMATION): Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity
\* Note: After 3 cycles of treatment, nivolumab administration may be decreased to once every 4 weeks in all cohorts, in consultation with the study principal investigator.
After completion of study treatment, patients are followed up monthly for 1 year.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: