Trial Title:
Tafasitamab and Zanubrutinib for the Treatment of Patients With Newly Diagnosed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, TaZA CLL Study
NCT ID:
NCT05718869
Condition:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Zanubrutinib
Immunoglobulins
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 (tafasitamab and zanubrutinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (tafasitamab and zanubrutinib)
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 (tafasitamab and zanubrutinib)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Tafasitamab
Description:
Given IV
Arm group label:
Treatment (tafasitamab and zanubrutinib)
Other name:
Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer
Other name:
Monjuvi
Other name:
MOR-00208
Other name:
MOR00208
Other name:
MOR208
Other name:
Tafasitamab-cxix
Other name:
XmAb5574
Intervention type:
Drug
Intervention name:
Zanubrutinib
Description:
Given PO
Arm group label:
Treatment (tafasitamab and zanubrutinib)
Other name:
BGB-3111
Other name:
Brukinsa
Other name:
BTK-InhB
Summary:
This phase II trial tests how well tafasitamab and zanubrutinib works in treating
patients with newly diagnosed chronic lymphocytic leukemia (CLL)/small lymphocytic
lymphoma (SLL). Tafasitamab is a monoclonal antibody that may interfere with the ability
of cancer cells to grow and spread. Zanubrutinib is in a class of medications called
kinase inhibitors. It works by blocking the action of a protein that signals cancer cells
to multiply. This may stop the growth and spread of cancer cells. Giving tafasitamab and
zanubrutinib in combination may kill more cancer cells in patients with CLL/SLL than
giving either treatment alone.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the safety/tolerability of tafasitamab and zanubrutinib (as assessed by
unacceptable toxicity) in patients with newly diagnosed CLL. (Safety lead-in) II. To
evaluate the anti-tumor activity of tafasitamab and zanubrutinib as assessed by complete
response (CR) rate per International Workshop on CLL (iwCLL) 2018 criteria in patients
with newly diagnosed CLL. (Phase 2)
SECONDARY OBJECTIVES:
I. To assess the toxicity of the combination of tafasitamab and zanubrutinib through
evaluation of toxicities.
II. To obtain estimates of overall response rate (ORR), progression-free survival (PFS),
and duration of response (DOR).
III. To assess the undetectable minimal residual disease (uMRD) rate in response to
tafasitamab and zanubrutinib.
EXPLORATORY OBJECTIVES:
I. To assess the effect of tafasitamab and zanubrutinib combination on immune function of
T cells and NK cells.
II. To explore mechanisms of resistance to the combination of tafasitamab and
zanubrutinib.
III. To investigate the association of established biomarkers (chromosomal abnormalities,
immunoglobulin heavy chain [IGHV] mutational status, TP53 mutational status) with
response (ORR and PFS) to tafasitamab and zanubrutinib in patients with CLL.
OUTLINE: This is a dose-escalation study of zanubrutinib followed by a phase II study.
Patients receive tafasitamab intravenously (IV) and zanubrutinib orally (PO) on study.
Patients also collection of blood samples on study and undergo computed tomography (CT)
scan and bone marrow biopsy throughout the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Age: >= 18 years
- Eastern Cooperative Oncology Group (ECOG) =< 2
- Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL as documented by
medical records and with histology based on criteria established by the World Health
Organization (WHO)
- No prior treatment for CLL, except steroids and/or rituximab to treat autoimmune
complications
- Active disease meeting criteria for requiring treatment per the iwCLL 2018
guidelines
- A minimum of any one of the following constitutional symptoms:
- Unintentional weight loss > 10% within the previous 6 months prior to
screening
- Extreme fatigue (unable to work or perform usual activities)
- Fevers of greater than 100.5 degrees Fahrenheit (F) for >= 2 weeks without
evidence of infection
- Night sweats without evidence of infection
- Evidence of progressive marrow failure as manifested by the development of, or
worsening of anemia or thrombocytopenia
- Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic
splenomegaly
- Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive
lymphadenopathy
- Progressive lymphocytosis with an increase of > 50% over a 2-month period, or
an anticipated doubling time of less than 6 months
- Autoimmune anemia or thrombocytopenia that is poorly responsive to
corticosteroids
- Symptomatic or functional extranodal involvement (eg, skin, kidney, lung,
spine)
- Participant must be able to swallow tablets or capsules. A participant with any
gastrointestinal disease that would impair ability to swallow, retain, or absorb
drug is not eligible
- Absolute neutrophil count (ANC) >= 1,000/mm^3 unless due to bone marrow involvement
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless
cytopenia is secondary to disease involvement
- Platelets >= 75,000/mm^3 unless due to bone marrow involvement, and independent of
transfusion support, with no active bleeding
- Direct bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease
or compensated hemolysis directly attributable to CLL)
- Aspartate aminotransferase (AST) =< 2.5 X ULN
- Alanine aminotransferase (ALT) =< 2.5 X ULN
- Estimated creatinine clearance of >= 30 mL/min using the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) formula
- IF NOT RECEIVING ANTICOAGULANTS: International normalized ratio (INR) OR prothrombin
(PT) =< 1.5 x ULN; IF ON ANTICOAGULANT THERAPY: PT must be within therapeutic range
of intended use of anticoagulants
- IF NOT RECEIVING ANTICOAGULANTS: Activated partial thromboplastin time (aPTT) =< 1.5
x ULN; IF ON ANTICOAGULANT THERAPY: aPTT must be within therapeutic range of
intended use of anticoagulants
- Women of childbearing potential (WOCBP): negative serum pregnancy test
- Agreement by females and males of childbearing potential to use an effective method
of birth control or abstain from heterosexual activity for the course of the study
through at least 3 months after the last dose of protocol therapy
- A woman is considered of childbearing potential, ie, fertile, following
menarche and until becoming postmenopausal unless permanently sterile.
Permanent sterilization methods include hysterectomy, bilateral salpingectomy,
and bilateral oophorectomy. Contraception methods include the following:
- Combined (estrogen- and progestogen- containing) hormonal contraception
associated with the inhibition of ovulation or oral, intravaginal, or
transdermal
- Progestogen-only hormonal contraception associated with the inhibition of
ovulation or oral, injectable, implantable
- An intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion vasectomized partner (provided that the
vasectomized partner is the sole sexual partner of the woman of
childbearing potential study participant and that the vasectomized partner
has received medical assessment of surgical success)
- Sexual abstinence (defined as refraining from heterosexual intercourse
during the entire period of risk associated with the study treatment,
starting the day prior to first dose of study drug, for the duration of
the study, and for >= 90 days after the last dose of zanubrutinib or
ibrutinib. Total sexual abstinence should only be used as a contraceptive
method if it is in line with the patients' usual and preferred lifestyle.
Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation
methods), declaration of abstinence for the duration of exposure to
investigational medicinal product, and withdrawal are not acceptable
methods of contraception. Of note, barrier contraception (including male
and female condoms with or without spermicide) is not considered a highly
effective method of contraception, and, if used, this method must be used
in combination with another acceptable method listed above. If patient is
using hormonal contraceptives such as birth control pills or devices, a
barrier method of contraception (eg, condoms) must also be used. A
postmenopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle-stimulating hormone level in
the postmenopausal range may be used to confirm a postmenopausal state in
women not using hormonal contraception or hormonal replacement therapy.
However, in the absence of 12 months of amenorrhea, a single
follicle-stimulating hormone measurement is insufficient
Exclusion Criteria:
- Chronic use of corticosteroids in excess of 20 mg/day prednisone or its equivalent
- Major surgery (under general anesthesia) within 30 days prior to therapy
- Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are
allowed
- Use of moderate or strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks of the
first day of study therapy. CYP3A inhibitors are allowed.
- For patients intended to enroll on dose level (DL) -1 use of strong CYP3A
inhibitors will be prohibited on-therapy and their use must be stopped at
minimum 2 weeks prior to the first day of study therapy
- Exposure to vaccination with live vaccine within 30 days prior to cycle 1 day 1
(C1D1), or anticipated need for such vaccination during treatment
- History of prior malignancy except:
- Malignancy treated with curative intent and no known active disease present for
>= 2 years prior to initiation of therapy on current study
- Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in
situ) without evidence of disease
- Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.)
without evidence of disease
- Asymptomatic prostate cancer managed with "watch and wait" strategy
- Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test
in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
- Known positive test result for SARS-CoV-2 unless follow-up test was negative or
investigator deems the infection is fully resolved
- Known positive test result for hepatitis C (hepatitis C virus [HCV] antibody
serology testing) and a positive test result for HCV ribonucleic acid (RNA).
Participants with positive serology are eligible in case of negative HCV RNA test
results
- Known positive test result for chronic hepatitis B virus (HBV) infection (defined by
hepatitis B virus surface antigen [HBsAg] positivity)
- Participants with occult or prior HBV infection (defined as negative HBsAg and
positive total hepatitis B core antibody) may be included if HBV
deoxyribonucleic acid (DNA) was undetectable, provided that they are willing to
undergo ongoing DNA testing.
- Antiviral prophylaxis may be administered as per institutional guidelines.
- Participants who have protective titers of HBsAb after vaccination or prior but
cured hepatitis B are eligible
- Known seropositive for or history of active viral infection with human
immunodeficiency virus (HIV)
- Clinically significant cardiovascular disease including the following:
- Myocardial infarction within 6 months before screening
- Unstable angina within 3 months before screening
- New York Heart Association class III or IV congestive heart failure
- History of clinically significant arrhythmias (eg, sustained ventricular
tachycardia, ventricular fibrillation, Torsades de Pointes)
- QTcF > 480 milliseconds based on Fridericia's formula
- History of Mobitz II second-degree or third-degree heart block without a
permanent pacemaker in place
- Known severe chronic obstructive pulmonary disease (COPD)
- Known hepatic cirrhosis or severe pre-existing hepatic impairment
- Major surgery (requiring general anesthesia) within 14 days before the first dose of
study drug or a scheduled surgery during study period
- Patients with clinically significant medical condition of malabsorption,
inflammatory bowel disease, chronic conditions which manifest with diarrhea,
refractory nausea, vomiting or any other condition that will interfere significantly
with drug absorption
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Mei
Phone:
626-218-2405
Email:
mamei@coh.org
Investigator:
Last name:
Matthew Mei
Email:
Principal Investigator
Facility:
Name:
City of Hope at Irvine Lennar
Address:
City:
Irvine
Zip:
92618
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Mei, MD
Phone:
626-218-2405
Email:
mamei@coh.org
Investigator:
Last name:
Matthew Mei, MD
Email:
Principal Investigator
Facility:
Name:
University of Miami Sylvester Comprehensive Cancer Center
Address:
City:
Miami
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Georgios Pongas, MD
Phone:
305-243-5302
Email:
gpongas@med.miami.edu
Investigator:
Last name:
Georgios Pongas, MD
Email:
Principal Investigator
Start date:
May 18, 2023
Completion date:
October 19, 2025
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05718869
