Trial Title:
Mosunetuzumab and Polatuzumab Vedotin for the Treatment of Patients with Relapsed or Refractory Grade 1-3a Follicular Lymphoma
NCT ID:
NCT06453044
Condition:
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3a Follicular Lymphoma
Refractory Grade 1 Follicular Lymphoma
Refractory Grade 2 Follicular Lymphoma
Refractory Grade 3a Follicular Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Recurrence
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Immunoconjugates
Polatuzumab vedotin
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 (mosunetuzumab, polatuzumab vedotin)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin)
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 (mosunetuzumab, polatuzumab vedotin)
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:
Biological
Intervention name:
Mosunetuzumab
Description:
Given SC
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin)
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:
Drug
Intervention name:
Polatuzumab Vedotin
Description:
Given IV
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin)
Other name:
ADC DCDS4501A
Other name:
Antibody-Drug Conjugate DCDS4501A
Other name:
DCDS4501A
Other name:
FCU 2711
Other name:
polatuzumab vedotin-piiq
Other name:
Polivy
Other name:
RG7596
Other name:
Ro 5541077-000
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary Studies
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin)
Summary:
This phase II trial tests how well mosunetuzumab and polatuzumab vedotin works in
treating patients with grade 1-3a follicular lymphoma that has come back after a period
of improvement (relapsed) or that has not responded to previous treatment (refractory).
Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer
cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, polatuzumab,
linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer
cells in a targeted way and delivers vedotin to kill them. Giving mosunetuzumab and
polatuzumab vedotin may kill more cancer cells in patients with relapsed or refractory
grade 1-3a follicular lymphoma.
Detailed description:
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of mosunetuzumab plus polatuzumab vedotin in
patients with relapsed/refractory (R/R) follicular lymphoma (FL). (Safety lead-in) II.
Estimate the complete response (CR) rate to mosunetuzumab plus polatuzumab vedotin in R/R
FL patients. (Phase II)
SECONDARY OBJECTIVES:
I. Estimate the overall response rate (ORR), time to first CR, time to best response,
duration of response (DOR), duration of response among CR (DORC), progression-free
survival (PFS), overall survival (OS), and quality of life (QOL) in R/R FL patients
treated with mosunetuzumab plus polatuzumab vedotin.
II. Evaluate the toxicity of mosunetuzumab plus polatuzumab vedotin for R/R FL. III.
Examine the use of tocilizumab for cytokine release syndrome (CRS) in R/R FL patients
treated with mosunetuzumab plus polatuzumab vedotin.
EXPLORATORY OBJECTIVES:
I. Assess baseline and on-treatment biomarkers, and evaluate association with anti-tumor
activity and safety.
II. Examine the type and incidence of CD20 gene mutations/ downregulation at relapse in
R/R FL patients treated with mosunetuzumab plus polatuzumab vedotin.
OUTLINE:
Patients receive polatuzumab vedotin intravenously (IV) over 30-90 minutes on day 1 of
each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease
progression or unacceptable toxicity. Patients also receive mosunetuzumab subcutaneously
(SC) on days 1, 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21
days for up to 8-17 cycles in the absence of disease progression or unacceptable
toxicity. Additionally, patients undergo blood sample collection and computed tomography
(CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
throughout the study.
After completion of study treatment, patients are followed up at 30 days and then for 3
years.
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 follicular lymphoma grade 1-3a according to
the World Health Organization (WHO) classification. Note: A history of diffuse large
B-cell lymphoma (DLBCL) and/or grade 3b follicular lymphoma is allowed (follicular
large B-cell lymphoma in the WHO 5th classification of mature B-cell lymphoma) but
these cannot be present at the time of study enrollment. Enrollment of any such
cases on this study must receive prior approval by the study PI
- Relapsed/ refractory disease after at least one prior line of therapy. Relapse must
have been confirmed histologically
- Tumor must be positive for CD20 by immunohistochemistry or flow cytometry after the
most recent therapy. Note: As a pan-B marker, CD79B+ is nearly always present and is
not a criterion for inclusion
- Active disease requiring treatment per treating physician's decision
- Radiographically measurable disease by Lugano criteria (e.g., one or more nodal
sites of disease ≥ 1.5 cm and/or at least one extranodal site of disease ≥ 1.0 cm in
longest dimension)
- Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior
anti-cancer therapy
- WITHOUT BONE MARROW INVOLVEMENT BY LYMPHOMA: Absolute neutrophil count (ANC) ≥
1,000/mm^3. NOTE: Growth factor is not permitted within 7 days of ANC assessment
unless cytopenia is secondary to disease involvement
- WITH BONE MARROW INVOLVEMENT BY LYMPHOMA AND/OR DISEASE-RELATED NEUTROPENIAS: ANC ≥
500/mm^3. NOTE: Growth factor is not permitted within 7 days of ANC assessment
unless cytopenia is secondary to disease involvement
- WITHOUT BONE MARROW INVOLVEMENT BY LYMPHOMA: Platelets ≥ 75,000/mm^3. NOTE: Platelet
transfusions are not permitted within 7 days of platelet assessment unless cytopenia
is secondary to disease involvement
- WITH BONE MARROW INVOLVEMENT BY LYMPHOMA AND/OR DISEASE-RELATED CYTOPENIAS:
Platelets ≥ 50,000/mm^3. NOTE: Platelet transfusions are not permitted within 7 days
of platelet assessment unless cytopenia is secondary to disease involvement
- Hemoglobin ≥ 8 g/dL. NOTE: Red blood cell transfusions are not permitted within 7
days of hemoglobin assessment unless cytopenia is secondary to disease involvement
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN). If hepatic involvement by
lymphoma, or Gilbert's disease: ≤ 3 x 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, 3 months after the last dose of
polatuzumab vedotin, and 3 months after the last dose of tocilizumab (if
applicable). 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 until 5 months after the last dose of polatuzumab vedotin, and
2 months after the last dose of tocilizumab (if applicable). 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 contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, established proper use of
hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine
devices, and copper intrauterine devices. The reliability of sexual abstinence
should be evaluated in relation to the duration of the clinical trial and the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal
are not acceptable methods of contraception
Exclusion Criteria:
- Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies.
Prior exposure to 2 or less doses without evidence of resistance is allowed
- Prior treatment with polatuzumab vedotin or with an antibody-drug conjugate
containing monomethyl auristatin E (MMAE). Prior exposure to 2 or less doses without
evidence of resistance is allowed
- Allogeneic stem cell transplant within 2 years prior to day 1 of protocol therapy,
requires immunosuppression, or has evidence of active-versus-host-disease
- Patients who had an allogeneic transplant > 2 years prior to day 1 of protocol
therapy must additionally have been stable off immunosuppressive agents for ≥ 2
months
- Autologous stem cell transplant within 100 days prior to day 1 of protocol therapy
- Chimeric antigen receptor (CAR)-T therapy within 30 days prior to day 1 of protocol
therapy
- Prior use of any anti-lymphoma treatment with monoclonal antibody,
radioimmunoconjugate or antineoplastic drug conjugate (ADC) within 4 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 4 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
- Live vaccine within 30 days prior to day 1 of protocol therapy
- Systemic immunosuppressive therapy (including, but not limited to, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF]
agents) with the exception of corticosteroid treatment for lymphoma symptom control
must be tapered down to ≤ 10 mg/day prednisone or equivalent 14 days prior to day 1
of protocol therapy. 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
- Use of 4 or less pulsed doses of steroids (i.e. dexamethasone) for urgent
stabilization of lymphoma or symptom management
- Grade ≥ 2 peripheral neuropathy
- History of severe allergic or anaphylactic reaction to humanized, chimeric or murine
monoclonal antibodies (or recombinant antibody-related fusion proteins)
- History of solid organ transplantation
- History of progressive multifocal leukoencephalopathy (PML)
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- Significant active pulmonary disease (e.g., bronchospasm and/or obstructive
pulmonary disease)
- Pneumonitis or interstitial lung disease requiring ongoing corticosteroid or
immunosuppression and/or requirement for supplemental oxygen
- Patients with any other history of pneumonitis or interstitial lung disease may
be eligible after discussion with the study PI
- Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or
polymerase chain reaction (PCR) test within 7 days prior to day 1 of protocol
therapy
- Clinically significant uncontrolled illness
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment or any major episode
of infection requiring treatment with IV antibiotics or hospitalization (relating to
the completion of the course of antibiotics) within 2 weeks prior to the first study
treatment administration
- 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 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 highly
active antiretroviral therapy (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
- Previously treated CNS involvement including disease with leptomeningeal
involvement, is acceptable. Patients should be neurologically stable prior to
study entry, and receiving a stable or decreasing corticosteroid dose
- History of CNS disease which was symptomatic or required treatment in the past 1
year, such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease
- Symptomatic cardiac disease such as New York Heart Association class III or IV
(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 systemic treatment
- History of autoimmune disease, including, but not limited to, myasthenia gravis,
myositis, autoimmune hepatitis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener granulomatosis, Guillain-Barré
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 rheumatoid arthritis, Sjögren syndrome, systemic
lupus erythematosus may be eligible after discussion with the study PI
- Patients with a history of disease-related immune thrombocytopenic purpura,
autoimmune hemolytic anemia, or other stable autoimmune diseases may be
eligible after discussion with the study PI
- 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)
- Concomitant investigational therapeutic therapy or within 7 days prior to initiation
of study treatment
- 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:
626-256-4673
Email:
mamei@coh.org
Contact backup:
Last name:
Matthew Mei
Facility:
Name:
City of Hope Orange County Lennar Foundation Cancer Center
Address:
City:
Irvine
Zip:
92618
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Azra Borogovac, MD
Phone:
949-844-1738
Email:
aborogovac@coh.org
Contact backup:
Last name:
Azra Borogovac, MD
Start date:
September 9, 2024
Completion date:
March 14, 2028
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/NCT06453044
