Trial Title:
Comparing the Effectiveness of the Immunotherapy Agents Rituximab or Mosunetuzumab in Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma
NCT ID:
NCT05886036
Condition:
Nodular Lymphocyte Predominant B-Cell Lymphoma
Recurrent Nodular Lymphocyte Predominant B-Cell Lymphoma
Refractory Nodular Lymphocyte Predominant B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Hodgkin Disease
Deoxyglucose
Rituximab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Fluorodeoxyglucose F18
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
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:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo PET/CT
Arm group label:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
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:
Other
Intervention name:
Fludeoxyglucose F-18
Description:
Receive FDG
Arm group label:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
Other name:
18FDG
Other name:
FDG
Other name:
Fludeoxyglucose (18F)
Other name:
fludeoxyglucose F 18
Other name:
Fludeoxyglucose F18
Other name:
Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
Other name:
Fluorodeoxyglucose F18
Intervention type:
Biological
Intervention name:
Mosunetuzumab
Description:
Given SC
Arm group label:
Arm I (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:
Arm I (Mosunetuzumab)
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
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:
Biological
Intervention name:
Rituximab
Description:
Given IV
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
Other name:
ABP 798
Other name:
BI 695500
Other name:
BI-695500
Other name:
BI695500
Other name:
Blitzima
Other name:
C2B8 Monoclonal Antibody
Other name:
Chimeric Anti-CD20 Antibody
Other name:
CT-P10
Other name:
IDEC 102
Other name:
IDEC-102
Other name:
IDEC-C2B8
Other name:
IDEC-C2B8 Monoclonal Antibody
Other name:
IDEC102
Other name:
Ikgdar
Other name:
Mabtas
Other name:
MabThera
Other name:
Monoclonal Antibody IDEC-C2B8
Other name:
PF 05280586
Other name:
PF-05280586
Other name:
PF05280586
Other name:
Riabni
Other name:
Ritemvia
Other name:
Rituxan
Other name:
Rituximab ABBS
Other name:
Rituximab ARRX
Other name:
Rituximab Biosimilar ABP 798
Other name:
Rituximab Biosimilar BI 695500
Other name:
Rituximab Biosimilar CT-P10
Other name:
Rituximab Biosimilar GB241
Other name:
Rituximab Biosimilar IBI301
Other name:
Rituximab Biosimilar JHL1101
Other name:
Rituximab Biosimilar PF-05280586
Other name:
Rituximab Biosimilar RTXM83
Other name:
Rituximab Biosimilar SAIT101
Other name:
Rituximab Biosimilar SIBP-02
Other name:
rituximab biosimilar TQB2303
Other name:
Rituximab PVVR
Other name:
Rituximab-abbs
Other name:
Rituximab-arrx
Other name:
Rituximab-blit
Other name:
Rituximab-pvvr
Other name:
Rituximab-rite
Other name:
Rituximab-rixa
Other name:
Rituximab-rixi
Other name:
Rixathon
Other name:
Riximyo
Other name:
RTXM 83
Other name:
RTXM-83
Other name:
RTXM83
Other name:
Ruxience
Other name:
Truxima
Intervention type:
Biological
Intervention name:
Rituximab and Hyaluronidase Human
Description:
Given SC
Arm group label:
Arm II (Rituximab, Rituximab and hyaluronidase human)
Other name:
Rituxan Hycela
Other name:
Rituximab Plus Hyaluronidase
Other name:
Rituximab/Hyaluronidase
Other name:
Rituximab/Hyaluronidase Human
Summary:
This phase II trial compares mosunetuzumab to the usual treatment (rituximab) for
improving survival in patients with nodular lymphocyte-predominant Hodgkin lymphoma
(NLPHL). Rituximab and mosunetuzumab are monoclonal antibodies. They bind to a protein
called CD20, which is found on B cells (a type of white blood cell) and some types of
cancer cells. This may help the immune system kill cancer cells. Mosunetuzumab may be
more effective at extending survival in patients with NLPHL than the usual approach with
rituximab.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare the progression-free survival (PFS) of mosunetuzumab versus rituximab in
NLPHL patients.
SECONDARY OBJECTIVES:
I. To compare the safety and antitumor activity of NLPHL patients treated with
mosunetuzumab versus rituximab.
II. To evaluate the molecular effects of mosunetuzumab and rituximab on tumor cells and
the immune response and identify biomarkers of response or resistance with ribonucleic
acid sequencing (RNAseq), whole exome sequencing (WES), immunohistochemistry (IHC) CD20,
PD-1, PD-L1, PD-L2.
III. To evaluate tumor microenvironment and peripheral immune status with single-cell
ribonucleic acid sequencing (scRNA-seq).
EXPLORATORY OBJECTIVES:
I. To evaluate CD20 expression and correlate with response. II. To evaluate the dynamic
molecular response of NLPHL patients treated with rituximab or mosunetuzumab with
circulating tumor deoxyribonucleic acid (ctDNA).
III. To evaluate the safety and efficacy (including tumor response, immune response, and
overall survival) of the crossover patients.
IV. To assess the association of baseline fludeoxyglucose F-18 (FDG)-positron emission
tomography/computed tomography (PET/CT) measurements including metabolic tumor volume
(MTV) and maximum standardized uptake value (SUVmax), in combination with other risk
factors, with PFS and overall survival (OS) in patients with lymphocyte-predominant
Hodgkin lymphoma treated with mosunetuzumab or rituximab.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive mosunetuzumab subcutaneously (SC) on days 1, 8, and 15 of cycle 1
and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 8 cycles in the
absence of disease progression or unacceptable toxicity. Patients who experience
progressive disease (PD) will be permitted to crossover to arm II at week 12. Patients
also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are
positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT on
study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood
sample collection throughout the trial. Patients may also undergo bone marrow biopsy and
tissue biopsy at end of treatment.
ARM II: Patients receive rituximab intravenously (IV) on day 1 and rituximab and
hyaluronidase human SC on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days
for up to 2 cycles 8 weeks apart in the absence of disease progression or unacceptable
toxicity. Patients may receive rituximab IV on days 8, 15, and 22 of each cycle if
rituximab and hyaluronidase human is not available. Patients who experience PD will be
permitted to crossover to arm I at week 12. Patients also receive FDG and undergo PET/CT
at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow
biopsy also receive FDG and undergo PET/CT on study. Patients also undergo bone marrow
biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial.
Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment.
After completion of study treatment, patients are followed up every 6 months for 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histopathologically confirmed diagnosis of NLPHL as confirmed by local pathologist's
expert review.
- Untreated NLPHL: stage IB to IV according to Cotswolds. The proportion of
patients with stages I or II treated with consolidative radiotherapy will be
capped at 40%.
- Previously treated NLPHL, any stage.
- According to the treating physician, the patient should not be observed and
needs therapy, notably because of B-symptoms (unexplained fever [temperature >
38 degrees Celsius (> 100.4 degrees Fahrenheit)], weight loss [unexplained loss
of > 10 percent of body weight over the past six months], or drenching night
sweats), symptomatic nodal or extranodal disease, or patient preferences.
- Patients must have measurable disease according to the Lugano/Lymphoma Response to
Immunomodulatory Therapy Criteria (LYRIC) classification.
- Age >= 18 years. Because no dosing or adverse event (AE) data are currently
available on the use of mosunetuzumab in patients < 18 years of age, children are
excluded from this study.
- Eastern Cooperative Oncology Group performance status =< 2 (Karnofsky >= 60%).
- Absolute neutrophil count >= 1,000/mcL.
- Platelets >= 100,000/mcL.
- Total bilirubin =< 1.5 institutional upper limit of normal (ULN), except in patients
with Gilbert's syndrome as defined by > 80% unconjugated bilirubin.
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase
[SGOT])/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) =< 3
x institutional ULN.
- Glomerular filtration rate (GFR) >= 40mL /min= GFR (mL/Min/1.73 m^2) * body surface
area (BSA)/1.73.
- Human immunodeficiency virus-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.
- The effects of mosunetuzumab on the developing human fetus are unknown. For this
reason and because other therapeutic agents used in this trial are known to be
teratogenic, women of childbearing potential and men must agree to use adequate
contraception (hormonal and/or barrier method of birth control; abstinence) (both
hormonal and barrier method of birth control are required for participants in
Canada) prior to study entry and for the duration of study participation. 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 and women treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 3
months after completion of mosunetuzumab administration and 12 months after
completion of rituximab administration.
- 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.
Exclusion Criteria:
- Classical Hodgkin lymphoma (cHL) or composite lymphoma.
- Transformed NLPHL, concerns of the treating physician of an occult transformation or
concerns of the treating physician that the patient needs cytotoxic therapy.
- Previous therapy with rituximab.
- Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have
residual toxicities > grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents.
- Patients with central nervous system (CNS) involvement as a result of lymphoma.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to mosunetuzumab or rituximab.
- 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 there is an unknown but
potential risk for AEs in nursing infants secondary to treatment of the mother with
mosunetuzumab; breastfeeding should be discontinued if the mother is treated with
mosunetuzumab or rituximab. These potential risks may also apply to other agents
used in this study.
- Prior allogeneic stem cell or solid organ transplantation.
- Participants who have received a live, attenuated vaccine within 4 weeks before
first dose of study treatment or anticipation that such a live, attenuated vaccine
will be required during the study. Participants must not receive live, attenuated
vaccines (e.g., FluMist [registered trademark]) while receiving study treatment and
after the last dose until B-cell recovery to the normal ranges. Killed vaccines or
toxoids should be given at least 4 weeks prior to the first dose of study treatment
to allow development of sufficient immunity.
- Any other anti-cancer therapy, whether investigational or approved, including but
not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever
is shorter, prior to initiation of study treatment.
- Evidence of any significant, concomitant disease that could affect compliance with
the protocol or interpretation of results as judged by the investigator, including,
but not limited to:
- Significant cardiovascular disease (e.g., New York Heart Association class III
or IV cardiac disease, myocardial infarction within the previous 6 months,
unstable arrhythmia, or unstable angina).
- Significant pulmonary disease (such as obstructive pulmonary disease or history
of bronchospasm).
- Current or past history of CNS disease, such as stroke, epilepsy, CNS
vasculitis, or neurodegenerative disease.
- Participants with a history of stroke who have not experienced a stroke or
transient ischemic attack in the past 1 year and have no residual neurologic
deficits as judged by the investigator are allowed.
- Participants with a history of epilepsy who have had no seizures in the past 2
years with or without anti-epileptic medications can be eligible only for the
expansion cohort.
- History of confirmed progressive multifocal leukoencephalopathy (PML).
- Participants with infections requiring IV treatment with antibiotics or
hospitalization (grade 3 or 4) within the last 4 weeks prior to enrollment or known
active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or
other infection (excluding fungal infections of nail beds) at study enrollment.
- Systemic immunosuppressive medications (including, but not limited to,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within 2 weeks prior to first dose of study treatment.
- Known or suspected chronic active Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
infection.
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center-Overland Park
Address:
City:
Overland Park
Zip:
66210
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Hospital-Westwood Cancer Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center - North
Address:
City:
Kansas City
Zip:
64154
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center - Lee's Summit
Address:
City:
Lee's Summit
Zip:
64064
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center at North Kansas City Hospital
Address:
City:
North Kansas City
Zip:
64116
Country:
United States
Status:
Suspended
Facility:
Name:
Memorial Sloan Kettering Basking Ridge
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Monmouth
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Bergen
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Commack
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Westchester
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Nassau
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Raphael E. Steiner
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-UC Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Suspended
Facility:
Name:
University of Cincinnati Cancer Center-West Chester
Address:
City:
West Chester
Zip:
45069
Country:
United States
Status:
Suspended
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Sami Ibrahimi
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Natalie Galanina
Email:
Principal Investigator
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
Dai Chihara
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Allison Bock
Email:
Principal Investigator
Facility:
Name:
Virginia Commonwealth University/Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CTOclinops@vcu.edu
Investigator:
Last name:
Bruce O. Hough
Email:
Principal Investigator
Start date:
January 23, 2024
Completion date:
October 31, 2026
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/NCT05886036
