Trial Title:
A Randomized Phase II Study Of Bruton Tyrosine Kinase Inhibitor With Or Without Venetoclax In Veterans With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT ID:
NCT06520098
Condition:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Venetoclax
Zanubrutinib
Acalabrutinib
Ibrutinib
Conditions: Keywords:
Leukemia, Lymphoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
The addition of Venetoclax to BTKi for 12 months in anticipated to improve both the
clinical response rates and the quality of life of patients as compared to indefinite use
of BTKi monotherapy in CLL/SLL patients
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia
(CLL) with 17p deletion, as detected by an FDA approved test, who have received at least
one prior therapy.
Arm group label:
Arm B : BTKi + Venetoclax for 12 cycles, then discontinue
Other name:
VENCLEXTA
Intervention type:
Drug
Intervention name:
Ibrutinib, Acalabrutinib, Zanubrutinib
Description:
IMBRUVICA is a kinase inhibitor Acalabrutinib is a selective, irreversible small molecule
inhibitor of BTK. Zanubrutinib is BTK inhibitors
Arm group label:
Arm A : Continue BTKi single agent
Arm group label:
Arm B : BTKi + Venetoclax for 12 cycles, then discontinue
Other name:
IMBRUVICA, CALQUENCE, BRUKINSA
Summary:
People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that
are taken by mouth. This type of pill is called "Bruton Tyrosine Kinase Inhibitor" or
BTKi. Another treatment for CLL/SLL is a different pill called venetoclax.
The purpose of this study is to compare continuing the current treatment with BTKi alone,
as long as it is working, to another arm of treatment which adds venetoclax to the
current treatment (BTKi), for one year. After one year, both pills in this arm of
treatment would be stopped and the participants will be closely monitored.
Detailed description:
People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that
are taken by mouth. This type of pill is called a "Bruton Tyrosine Kinase Inhibitor" or
BTKi. Another treatment for CLL/SLL is a different pill called venetoclax.
People with CLL/SLL who are currently taking BTKi as their treatment must continue to
take the medicine for the rest of their lives (unless it is no longer working or causing
difficult side effects).
New studies tested the combination of BTKi and venetoclax for one to two years, and
showed that it was a very effective treatment, and allowed patients to stop therapy.
The investigators don't know if adding venetoclax in patients who have already taken BTKi
therapy for at least six months and who are responding to it will help control the
CLL/SLL better and if it will allow them to stop treatment safely. Also, the
investigators don't know how the side effects and effectiveness of the combination will
be in Veterans. The investigators also don't know how a patient's quality of life will be
affected if they continue BTKi by itself or if they take the combination and then are
able to stop treatment.
If participants meet the eligibility criteria, they will be randomly assigned a study
treatment. This study has 2 main study groups:
ARM A (BTKI ALONE): There will be about 50 people in this group.
ARM B (BTKI PLUS VENETOCLAX): There will be about 50 people in this group.
The participants will not be charged for any treatments or procedures that are part of
this study. If participants usually pay co-payments for VA care and medications, they
will still pay these co-payments for VA care and medications that are not part of this
study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- CLL or SLL diagnosis
- Patients must have been diagnosed with CLL (> 5000 B-cells per uL of peripheral
blood at any point during the course of their disease) or small lymphocytic lymphoma
(SLL) with <5000 B-cells per µL of blood but with disease-associated lymphadenopathy
by 2018 IWCLL criteria.
- Prior treatment
- Patients must be currently receiving CLL/SLL directed therapy with a BTKi (i.e.,
ibrutinib, acalabrutinib, zanubrutinib) for at least six months.
- The dose of BTKi must be stable for at least the past three months.
- Age 18 years
- ECOG performance status 0-2
- Detectable or measurable CLL/SLL in blood or imaging during the screening period.
Detectable CLL/SLL in the blood is defined either by elevation in absolute lymphocyte
count or by diagnostic flow cytometry from blood demonstrating presence of CLL cells.
- Low TLS risk, defined as having all lymph nodes less than 5 cm in diameter
(radiographically) and absolute lymphocyte count less than 25 x 109/L in blood,
within 30 days of enrollment.
- Required initial laboratory values
- Absolute Neutrophil Count (ANC) 1,000/mm3 except if due to bone marrow involvement
- Platelet Count (untransfused) 30,000/mm3 except if due to bone marrow involvement
- Calc. Creatinine Clearance 40 mL/min (by Cockcroft-Gault)
- Bilirubin 1.5 x upper limit of normal (ULN) except if due to liver involvement,
hemolysis, or Gilbert's disease
- AST / ALT 2.5 x upper limit of normal (ULN) except if due to liver involvement
- Other
- Patients must be able to swallow oral medications and not have the following
conditions: disease significantly affecting gastrointestinal absorption, resection
of the stomach or small bowel, partial or complete bowel obstruction.
- Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase
Exclusion Criteria:
- Prior treatment
- Patients must not have progression of CLL/SLL on BTKi therapy prior to initiation of
the study therapy.
- Patients must not have received the combination of BTKi + venetoclax previously.
- Comorbid conditions or other active diseases
- Patients must not have any history of Richter's transformation or prolymphocytic
leukemia.
- If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be
undetectable and be on suppressive therapy, if indicated.
- Please note: IVIG can cause a false positive hepatitis B serology. If patients
receiving routine IVIG have core antibody or surface antigen positivity without
evidence of active viremia (negative hepatitis B DNA) they may still participate in
the study, must have hepatitis serologies and hepatitis B DNA monitored periodically
by the treating physician.
- If history of hepatitis C virus (HCV) infection, must be treated with undetectable
HCV viral load.
- Patients with Class III or Class IV heart failure by New York Heart Association,
those with unstable angina, and those with uncontrolled arrhythmia are not eligible.
- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
therapy are eligible for this trial.
- Concomitant medications
- Patients must not be receiving active systemic anticoagulation with heparin or
warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior
to registration on the study.
- Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not recommended
on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14
days prior to registration on the study or discuss with the study principal
investigator.
- Chronic concomitant treatment with strong CYP3A4/5 inducers is not recommended.
Patients must discontinue the drug 14 days prior to registration on the study or
discuss with the study principal investigator.
- Patients must not require more than 20 mg prednisone or equivalent corticosteroid
daily.
- Patients must not have uncontrolled active systemic infection requiring intravenous
antibiotics
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
San Francisco VA Medical Center, San Francisco, CA
Address:
City:
San Francisco
Zip:
94121-1563
Country:
United States
Contact:
Last name:
Gerald Hsu, MD
Phone:
415-221-4810
Phone ext:
24343
Email:
gerald.hsu@va.gov
Facility:
Name:
Kansas City VA Medical Center, Kansas City, MO
Address:
City:
Kansas City
Zip:
64128-2226
Country:
United States
Contact:
Last name:
Murali K Nittala, MBBS MS MD
Phone:
816-861-4700
Phone ext:
57840
Email:
murali.nittala@va.gov
Investigator:
Last name:
Suman Kambhampati, MD MBBS
Email:
Principal Investigator
Facility:
Name:
Durham VA Medical Center, Durham, NC
Address:
City:
Durham
Zip:
27705-3875
Country:
United States
Contact:
Last name:
Daphne Friedman, MD
Phone:
919-286-0411
Email:
VHADURCancertrials@va.gov
Facility:
Name:
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Address:
City:
Seattle
Zip:
98108-1532
Country:
United States
Contact:
Last name:
Jeannine Barton
Phone:
206-277-3101
Email:
Jeannine.Barton@va.gov
Start date:
January 1, 2025
Completion date:
December 31, 2030
Lead sponsor:
Agency:
VA Office of Research and Development
Agency class:
U.S. Fed
Source:
VA Office of Research and Development
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06520098
