Trial Title:
Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
NCT ID:
NCT05672251
Condition:
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Grade 3b Follicular Lymphoma
Recurrent High Grade B-Cell Lymphoma
Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Recurrent Transformed Chronic Lymphocytic Leukemia
Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Refractory Grade 3b Follicular Lymphoma
Refractory High Grade B-Cell Lymphoma
Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Refractory Transformed Chronic Lymphocytic Leukemia
Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Recurrence
Loncastuximab tesirine
Antibodies, Bispecific
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:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
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:
Loncastuximab Tesirine
Description:
Given IV
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
Other name:
ADC ADCT-402
Other name:
ADCT-402
Other name:
Anti-CD19 PBD-conjugate ADCT-402
Other name:
Loncastuximab Tesirine-lpyl
Other name:
Zynlonta
Intervention type:
Biological
Intervention name:
Mosunetuzumab
Description:
Given IV
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
Other name:
Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A
Other name:
BTCT 4465A
Other name:
BTCT-4465A
Other name:
BTCT4465A
Other name:
CD20/CD3 BiMAb BTCT4465A
Other name:
Lunsumio
Other name:
Mosunetuzumab-axgb
Other name:
RG 7828
Other name:
RG-7828
Other name:
RG7828
Other name:
RO7030816
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (oncastuximab tesirine, mosunetuzumab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Summary:
This phase II trial studies the safety and how well of loncastuximab tesirine when given
together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma
that has come back (relapsed) or does not respond to treatment (refractory).
Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent
called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and
delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere
with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with
mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell
lymphoma.
Detailed description:
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of loncastuximab tesirine plus mosunetuzumab in
patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). (Safety
Lead-In) II. Estimate the overall response rate (ORR) in R/R DLBCL patients treated with
loncastuximab tesirine plus mosunetuzumab. (Phase 2)
SECONDARY OBJECTIVES:
I. Estimate the complete response (CR) rate, duration of response (DOR), progression-free
survival (PFS), and overall survival (OS) in R/R DLBCL patients treated with
loncastuximab tesirine plus mosunetuzumab.
II. Evaluate the toxicity of loncastuximab tesirine plus mosunetuzumab for R/R DLBCL.
EXPLORATROY OBJECTIVE:
I. Evaluate genomic and immune biomarkers of response and resistance to loncastuximab
tesirine combined with mosunetuzumab
OUTLINE:
Patients receive loncastuximab tesirine intravenously (IV) and mosunetuzumab IV on study.
Patients also undergo positron emission tomography (PET)/computed tomography (CT) scan,
biopsy, and collection of blood samples on study.
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.
- Be willing to provide tissue from a fresh core or excisional biopsy (performed as
standard of care) of a tumor lesion prior to starting study therapy or from
diagnostic tumor biopsies.
- If unavailable, exceptions may be granted with study principal investigator
(PI) approval.
- Age: >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) =< 2.
- Histologically confirmed diagnosis of diffuse large B-cell lymphoma or Follicular
Lymphoma Grade 3B according to the World Health Organization (WHO) classification,
with hematopathology review at the participating institution. Subtypes of DLBCL
including transformed indolent lymphomas (TIL) including Richter's Transformation,
primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma
not otherwise specified (HGBCL-NOS) are eligible.
- Life expectancy > 12 months.
- Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) or
follicular lymphoma Grade 3B according to the WHO classification, with
hematopathology review at the participating institution. Subtypes of DLBCL including
transformed indolent lymphomas (TIL) including Richter's Transformation, primary
mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not
otherwise specified (HGBCL-NOS) are eligible.
- Relapsed or refractory disease after >= 1 prior line of therapy (prior CD19-directed
therapy and prior autologous stem cell transplant are allowed).
- Relapse at the time of study enrollment must have been confirmed histologically
(with hematopathology review at the participating institution). Exceptions may
be granted with study PI approval.
- Measurable disease by computerized tomography (CT) or positron emission tomography
(PET)/CT scan with one or more sites of disease >= 1.5 cm in longest dimension.
- Tumor must be positive for both CD19 and CD20 by immunohistochemistry after the most
recent therapy.
- Fully recovered from the acute toxic effects (except alopecia) to =< Grade 1 to
prior anti-cancer therapy
- Without bone marrow involvement: Absolute neutrophil count (ANC) >= 1,000/mm^3.
- (G-CSF is allowed to reach ANC requirement).
- With bone marrow involvement: no minimum ANC requirement.
- (G-CSF is allowed to reach ANC requirement).
- Platelets >= 75,000/mm^3.
- Total bilirubin =< 1.5 X upper limit of normal (ULN).
- If hepatic involvement by lymphoma, or Gilbert's disease: =< 3X ULN.
- Aspartate aminotransferase (AST) =< 2.5 x ULN.
- If hepatic involvement by lymphoma: AST =< 5 x ULN.
- Alanine aminotransferase (ALT) =< 2.5 x ULN.
- If hepatic involvement by lymphoma: ALT =< 5 x ULN .
- Creatinine clearance of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gault
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 urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
- Agreement by females of childbearing potential to abstain from heterosexual
intercourse or use two adequate method of birth control, including at least 1 method
with a failure rate of < 1% per year, for at least 28 days prior to Day 1 of Cycle
1, during the treatment period (including periods of treatment interruption), until
3 months after the final dose mosunetuzumab and 9 months after the last dose of
loncastuximab tesirine. Women must refrain from donating eggs during this same
period. Agreement by males to abstain from heterosexual intercourse or use a condom
with female partners of childbearing potential or pregnant female partners during
the treatment period and for 3 months after the final dose of mosunetuzumab and 6
months after the last dose of loncastuximab tesirine. Men must refrain from donating
sperm during this same period.
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only) with no
identified cause other than menopause.
- Examples of non-hormonal contraceptive methods with a failure rate of < 1% per
year include bilateral tubal ligation, male sterilization, established and
proper use of progestogen only hormonal contraceptives that inhibit ovulation,
hormone releasing intrauterine devices, and copper intrauterine devices.
Barrier methods must always be supplemented with the use of a spermicide. Note:
Combined oral contraceptives are not recommended.
Exclusion Criteria:
- Prior treatment with loncastuximab tesirine.
- Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies.
- Prior allogeneic stem cell transplantation.
- Prior use of any monoclonal antibody, radioimmunoconjugate or ADC within 2 weeks
prior to Day 1 of protocol therapy.
- Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer
agent (investigational or otherwise) within 2 weeks or 5 half-lives of the drug,
whichever is shorter, prior to Day 1 of protocol therapy.
- Treatment with radiotherapy within 2 weeks prior to Day 1 of protocol therapy.
- If patients have received radiotherapy within 4 weeks prior to prior to Day 1
of protocol therapy, patients must have at least one measurable lesion outside
of the radiation field. Patients who have only one measurable lesion that was
previously irradiated but subsequently progressed are eligible.
- Autologous stem cell transplantation (SCT) within 30 days prior to prior to Day 1 of
protocol therapy.
- Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days
prior to Day 1 of protocol therapy.
- Live vaccine within 30 days prior to Day 1 of protocol therapy.
- Concomitant investigational therapy.
- Treatment-emergent immune-related adverse events associated with prior
immunotherapeutic agents(e.g., immune checkpoint inhibitor therapies). Note: For
certain prior treatments, such as CAR-T cell therapies, patients with prior
immune-related Grade >= 3 adverse events (e.g., CRS) may be allowed after discussion
with and approval by the Study PI.
- Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma
symptom control must be tapered down to =< 20 mg/day prednisone or equivalent.
Exceptions are:
- Inhaled or topical steroids
- Use of mineralocorticoids for management of orthostatic hypotension
- Use of physiologic doses of corticosteroids for management of adrenal
insufficiency
- Known hypersensitivity to biopharmaceutical produced in chinese hamster ovary (CHO)
cells or history of allergic reactions attributed to compounds of similar chemical
or biologic composition to study agents.
- Clinically significant third space fluid accumulation (i.e., ascites requiring
drainage or pleural effusion that is either requiring drainage or associated with
shortness of breath).
- History of solid organ transplantation.
- History of progressive multifocal leukoencephalopathy (PML).
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
- Clinically significant uncontrolled illness.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment.
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients
with past HBV infection (defined as negative hepatitis B surface antigen [HBsAg] and
positive hepatitis B core antibody [HBcAb]) are eligible if HBV deoxyribonucleic
acid (DNA) is undetectable. Patients who are positive for HCV antibody are eligible
if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
Testing to be done only in patients suspected of having infections or exposures.
- Known active human immunodeficiency virus (HIV) infection. Subjects who have an
undetectable or unquantifiable HIV viral load with CD4 > 200 and are on HAART
medication are allowed. Testing to be done only in patients suspected of having
infections or exposures.
- Known or suspected chronic active Epstein-Barr virus (EBV) infection.
- Known active central nervous system (CNS) involvement by lymphoma, including
leptomeningeal involvement.
- History of erythrema multiforme, Grade >= 3 rash, or blistering following prior
treatment with immunomodulatory derivatives.
- Symptomatic cardiac disease (including symptomatic ventricular dysfunction,
symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular
event/stroke or myocardial infarction within the past 6 months.
- Clinically significant history of liver disease, including viral or other hepatitis,
or cirrhosis.
- Active autoimmune disease requiring treatment.
- History of autoimmune disease, including, but not limited to, myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis.
- Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study.
- Patients with a history of disease-related immune thrombocytopenic purpura,
autoimmune hemolytic anemia, or other stable autoimmune diseases may be
eligible.
- Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than
for diagnosis.
- History of another primary malignancy that has not been in remission for at least 2
years, with the following exceptions:
- 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) without
evidence of disease
- Asymptomatic prostate cancer managed with a watch-and-wait strategy
- If the malignancy is expected to not require any treatment for at least 2 years
(this exception should be discussed with the study PI).
- 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:
Swetha Kambhampati
Phone:
626-256-4673
Phone ext:
82405
Email:
skambhampati@coh.org
Investigator:
Last name:
Swetha Kambhampati
Email:
Principal Investigator
Start date:
January 2, 2024
Completion date:
December 28, 2024
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/NCT05672251
