Ignite Creation Date:
2024-05-06 @ 2:03 PM
Last Modification Date:
2024-10-26 @ 1:24 PM
Study NCT ID:
NCT04209621
Status:
TERMINATED
Last Update Posted:
2022-03-09
First Post:
2019-12-21
Brief Title:
Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma CLLSLL
Status:
TERMINATED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to unexpected sudden death on study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Chronic lymphocytic leukemia CLL and small lymphocytic lymphoma SLL are cancers often treated with the drug ibrutinib For some people ibrutinib stops working Researchers want to see if adding another drug can help
Objective
To test how people with ibrutinib-resistant CLL respond to duvelisib
Eligibility
People ages 18 and older with CLL or SLL that is no longer responding to ibrutinib or has developed mutations that could stop it from working
Design
Participants will be screened with
Medical history
Physical exam
Heart tests
Blood and urine tests
CT scan For this participants will have a dye injected into a vein They will lie in a machine that takes pictures of the body
Bone marrow biopsy For this a needle injected into the participant s bone will remove marrow
Optional lymph node biopsy For this the participants whole lymph node or part of it will be removed through the skin
Optional lymphapheresis For this the participants blood is removed through a vein in one arm the white blood cells separated out and the blood returned through a vein in the other arm
Participants will take duvelisib twice daily by mouth They will continue ibrutinib at their current dose for the first 6 months They will continue to take duvelisib until their CLLSLL stops responding or they develop intolerable side effects
Participants will take an antibiotic and antiviral medication They may take steroids
Participants will have blood tests every 2 weeks during the first 2 months
Participants will have monthly follow-up visits during the first 6 months and every 3 months thereafter These will include repeats of some of the screening tests
Chronic lymphocytic leukemia CLL and small lymphocytic lymphoma SLL are cancers often treated with the drug ibrutinib For some people ibrutinib stops working Researchers want to see if adding another drug can help
Objective
To test how people with ibrutinib-resistant CLL respond to duvelisib
Eligibility
People ages 18 and older with CLL or SLL that is no longer responding to ibrutinib or has developed mutations that could stop it from working
Design
Participants will be screened with
Medical history
Physical exam
Heart tests
Blood and urine tests
CT scan For this participants will have a dye injected into a vein They will lie in a machine that takes pictures of the body
Bone marrow biopsy For this a needle injected into the participant s bone will remove marrow
Optional lymph node biopsy For this the participants whole lymph node or part of it will be removed through the skin
Optional lymphapheresis For this the participants blood is removed through a vein in one arm the white blood cells separated out and the blood returned through a vein in the other arm
Participants will take duvelisib twice daily by mouth They will continue ibrutinib at their current dose for the first 6 months They will continue to take duvelisib until their CLLSLL stops responding or they develop intolerable side effects
Participants will take an antibiotic and antiviral medication They may take steroids
Participants will have blood tests every 2 weeks during the first 2 months
Participants will have monthly follow-up visits during the first 6 months and every 3 months thereafter These will include repeats of some of the screening tests
Detailed Description:
Background
In chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL ibrutinib resistance is predominantly caused by somatic mutations in BTK and PLCG2 Virtually all patients with detectable mutations eventually develop progressive disease Patients who discontinue ibrutinib often have rapidly progressive disease that can be difficult to control These observations suggest that BTK inhibitors still exert at least a partial anti-tumor effect Outcomes after ibrutinib discontinuation are poor Early detection of BTK and PLCG2 mutations represents an opportunity for preemptive intervention to eliminate the resistant clone
Duvelisib is a dual PI3K-gamma and delta inhibitor Duvelisib monotherapy improved progression-free survival and overall response rate compared to ofatumumab and had a manageable safety profile in subjects with previously treated CLLSLL Based on these results duvelisib received US approval for CLLSLL after at least 2 prior therapies
This study will assess duvelisib in patients who develop disease progression or BTK andor PLCG2 mutations on ibrutinib Duvelisib will overlap with ibrutinib for the first six 28-day cycles to prevent disease acceleration often seen in patients who discontinue ibrutinib
Primary Objective
-To investigate the rate of overall response to duvelisib in patients with ibrutinib-resistant CLL
Key Eligibility Criteria
Patients on current treatment for CLLSLL with ibrutinib and at least one of the following
BTK andor PLCG2 mutations
Progressive CLL per CLL guidelines
Patients with known Richter transformation will be excluded
Design
This is a single-center single-arm open-label phase 2 study with a safety lead-in cohort
Treatment plan Duvelisib will be administered with ibrutinib for the first six 28-day cycles then duvelisib monotherapy will be administered continuously until disease progression or intolerance
Study Duration 5 years
Participant Duration until disease progression or intolerance
In chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL ibrutinib resistance is predominantly caused by somatic mutations in BTK and PLCG2 Virtually all patients with detectable mutations eventually develop progressive disease Patients who discontinue ibrutinib often have rapidly progressive disease that can be difficult to control These observations suggest that BTK inhibitors still exert at least a partial anti-tumor effect Outcomes after ibrutinib discontinuation are poor Early detection of BTK and PLCG2 mutations represents an opportunity for preemptive intervention to eliminate the resistant clone
Duvelisib is a dual PI3K-gamma and delta inhibitor Duvelisib monotherapy improved progression-free survival and overall response rate compared to ofatumumab and had a manageable safety profile in subjects with previously treated CLLSLL Based on these results duvelisib received US approval for CLLSLL after at least 2 prior therapies
This study will assess duvelisib in patients who develop disease progression or BTK andor PLCG2 mutations on ibrutinib Duvelisib will overlap with ibrutinib for the first six 28-day cycles to prevent disease acceleration often seen in patients who discontinue ibrutinib
Primary Objective
-To investigate the rate of overall response to duvelisib in patients with ibrutinib-resistant CLL
Key Eligibility Criteria
Patients on current treatment for CLLSLL with ibrutinib and at least one of the following
BTK andor PLCG2 mutations
Progressive CLL per CLL guidelines
Patients with known Richter transformation will be excluded
Design
This is a single-center single-arm open-label phase 2 study with a safety lead-in cohort
Treatment plan Duvelisib will be administered with ibrutinib for the first six 28-day cycles then duvelisib monotherapy will be administered continuously until disease progression or intolerance
Study Duration 5 years
Participant Duration until disease progression or intolerance
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-H-0016 | None | None | None |