Trial Title:
Venetoclax for the Treatment of Patients With Relapsed Hairy Cell Leukemia
NCT ID:
NCT06311227
Condition:
Recurrent Hairy Cell Leukemia
Recurrent Hairy Cell Leukemia Variant
Conditions: Official terms:
Leukemia
Leukemia, Hairy Cell
Recurrence
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (venetoclax)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (venetoclax)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (venetoclax)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (venetoclax)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (venetoclax)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
Treatment (venetoclax)
Other name:
ABT 199
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC 0199
Other name:
GDC-0199
Other name:
GDC0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Summary:
This phase II trial tests how well venetoclax works in treating patients with hairy cell
leukemia that has come back after a period of improvement (relapsed). Venetoclax is in a
class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth
of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR) of venetoclax.
SECONDARY OBJECTIVES:
I. To determine the complete remission (CR) and minimal residual disease (MRD)-negative
CR rates of venetoclax in relapsed hairy cell leukemia/hairy cell leukemia variant
(HCL/HCLv).
II. To determine the rates of MRD-negative by blood flow cytometry with venetoclax.
III. To determine the safety of venetoclax in relapsed HCL/HCLv. IV. To determine the
response and CR duration and MRD-negative survival in relapsed HCL/HCLv receiving
venetoclax.
EXPLORATORY OBJECTIVES:
I. To correlate response to TP53 mutations and other mutations, particularly for BRAF
wild-type (WT) relapsed HCL/HCLv.
II. To perform whole exome sequencing (WES) of relapsed HCL/HCLv samples to look for
mutations, to correlate with response.
OUTLINE:
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle.
Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression
or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance
imaging (MRI) and blood sample collection throughout the study. Patients may undergo bone
marrow biopsy and/or aspiration on study.
After completion of study treatment, patients are followed up at 30 days.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed HCL/HCLv after purine
analog therapy who are relapsed from or are ineligible for BRAF therapy and have not
received prior venetoclax
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Total bilirubin ≤ 3 x institutional upper limit of normal (ULN) unless consistent
with Gilbert's (ration between total and direct bilirubin > 5)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
≤ 3 × institutional ULN
- Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min/1.73m^2
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- Patients must have had no HCL/HCLv treatment for ≥ 4 weeks prior to enrollment, and
those with treatment > 4 weeks prior to enrollment must not be responding to their
last treatment with decreasing tumor burden or improving drug-related cytopenias
- Patients must have a need for treatment due to absolute neutrophil count (ANC) <
1/nL, hemoglobin (Hgb) < 10g/dL, platelets (Plt) < 100/nL, symptomatic splenomegaly,
enlarging HCL mass > 2cm in short axis, enlarging HCL mass > 0.5 cm in the central
nervous system (CNS) in short axis, or leukemic count > 5/nL
- The effects of venetoclax on the developing human fetus are unknown. For this
reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) during
treatment and for 30 days after the last dose of venetoclax. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately. Men treated or
enrolled on this protocol must also agree to use adequate contraception during
treatment and for 30 days after the last dose of venetoclax
- Ability to understand and the willingness to sign a written informed consent
document. Legally authorized representatives may sign and give informed consent on
behalf of study participants
- Ability and willingness to swallow pills
Exclusion Criteria:
- Patients who have received prior venetoclax
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to venetoclax
- Patients with uncontrolled intercurrent illness or any other significant
condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because venetoclax is a B-cell
lymphoma-2 (BCL-2) inhibitor agent with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with venetoclax,
breastfeeding should be discontinued if the mother is treated with venetoclax
- Malabsorption syndrome or other conditions that would interfere with intestinal
absorption
- Live attenuated vaccines should not be administered within 4 weeks prior to, during,
or 30 days after study treatment and recovery has occurred
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Institute LAO
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
Robert J. Kreitman
Email:
kreitmar@mail.nih.gov
Investigator:
Last name:
Robert J. Kreitman
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-UC Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Zulfa Omer
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Kerry A. Rogers
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-West Chester
Address:
City:
West Chester
Zip:
45069
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Zulfa Omer
Email:
Principal Investigator
Start date:
February 14, 2025
Completion date:
May 20, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06311227