Trial Title:
Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma
NCT ID:
NCT06594939
Condition:
Diffuse Large B Cell Lymphoma (DLBCL)
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Prednisone
Cyclophosphamide
Doxorubicin
Polatuzumab vedotin
Conditions: Keywords:
Mosunetuzumab
Polatuzumab vedotin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Polatuzumab Vedotin
Description:
A combination of a monoclonal antibody and a chemotherapy drug.
Arm group label:
Mosum-Pola-SD-CHP
Other name:
Polivy
Intervention type:
Drug
Intervention name:
Mosunetuzumab
Description:
A monoclonal antibody.
Arm group label:
Mosum-Pola-SD-CHP
Other name:
Lunsumio
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Chemotherapy drug, alkylating agent.
Arm group label:
Mosum-Pola-SD-CHP
Other name:
Cytoxan
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Chemotherapy drug, anthracycline antibiotic.
Arm group label:
Mosum-Pola-SD-CHP
Other name:
Adriamycin
Intervention type:
Drug
Intervention name:
Prednisone
Description:
Steroid, anti-inflammatory
Arm group label:
Mosum-Pola-SD-CHP
Intervention type:
Other
Intervention name:
Pegfilgrastim
Description:
Granulocyte stimulating factor, biologic response modifier.
Arm group label:
Mosum-Pola-SD-CHP
Other name:
filgrastim
Summary:
This single-arm, interventional phase 2 study is designed to evaluate whether the
inclusion of mosunetuzumab subcutaneous and polatuzumab vedotin (Mosun-Pola) to a
split-dose CHP chemotherapy backbone will improve outcomes for elderly patients with a
new diagnosis of diffuse large B-cell lymphoma.
Detailed description:
This trial combines two novel agents, mosunetuzumab subcutatneous and polatuzumab vedotin
(Mosun-Pola), with cytotoxic chemotherapy while allowing de-escalation in rapidly
responding patients. After completing the first two cycles of Mosun-Pola-SD-CHP therapy,
subjects will undergo an interim response assessment with positron emission tomography
(PET) / computed tomography (CT) and minimal residual disease (MRD) testing (ClonoSEQ;
Adaptive Biotechnology) prior to Cycle 3A. Patients who are interim PET-negative and
MRD-negative will be placed on an abbreviated treatment regimen, where they will receive
Mosun-Pola-SD-CHP therapy for only four cycles.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients aged 70-74 who are determined to be unfit or frail by the Cumulative
Illness Rating Scale-Geriatric (CIRS-G) score with 5-8 comorbid conditions scored 2
or more than 1 comorbidity scored 3-4 are allowed.
2. Newly diagnosed, untreated, biopsy-proven CD20 positive diffuse large B-cell
lymphoma (DLBCL) (including high-grade B-cell lymphoma and T-cell/histiocyte-rich
large B-cell lymphoma). Patients with discordant bone marrow (i.e., involved by
low-grade/indolent non-Hodgkin lymphoma) are eligible. Patients with transformed
DLBCL from underlying low-grade disease are eligible. Patients with composite DLBCL
and concurrent low-grade lymphoma are eligible. Patients with prior treatment for
low-grade NHL with non-anthracycline based regimens are eligible.
a. Short-course prednisone or equivalent steroid for symptom management is allowable
for up to seven days.
3. Measurable disease by positron emission tomography (PET) / computed tomography (CT)
using the Lugano criteria (lymph node >1.5 cm or extranodal site >1.0 cm).
4. Adequate biospecimen sample that meets current Adaptive Clonality ID Test specimen
requirements for DLBCL.
a. Note: the preferred ID specimen type is a formalin-fixed paraffin-embedded (FFPE)
lymph node biopsy, either FFPE slides or scrolls, targeting 40 microns of material.
5. Left ventricular ejection fraction ≥50% by echocardiography or multigated
acquisition (MUGA) scan.
6. Karnofsky Performance Score ≥50 or Eastern Cooperative Oncology Group (ECOG) scan
0-2.
7. Ann Arbor Stage II bulky, III, or IV disease.
8. Minimum life expectancy greater than 3 months (should be explicitly documented by
the enrolling investigator).
9. Negative HIV test. Individuals with a positive HIV test at screening are eligible
provided that, prior to enrollment, they are stable on antiretroviral therapy for at
least 4 weeks, have a CD4 count ≥200/µL, and have an undetectable viral load, and
have not had a history of opportunistic infection attributable to acquired
immunodeficiency syndrome (AIDS) within the last 12 months.
10. For patients with hepatitis B virus antigen (HBsAg) or core antibody (HBcAb)
seropositivity, patients must have a negative hepatitis B viral load and an
appropriate prophylaxis plan must be in place during chemotherapy therapy treatment.
For all patients that are hepatitis B core antibody positive, they should take
entecavir prophylaxis (0.5 mg by mouth daily) until 1 year from completion of
chemotherapy. Hepatitis B viral load should be checked on these patients prior to
starting chemotherapy and every 3 months thereafter if initial hepatitis B viral
load is negative (±1 week if chemotherapy cycle is delayed). If hepatitis B viral
load is positive, hepatology or ID referral is recommended, and hepatitis B viral
load should be checked monthly and every 3 months for 12 months after end of
treatment.
11. For patients with hepatitis C Ab positivity, a viral load must be checked and
negative for enrollment.
12. Negative SARS-CoV-2 antigen or polymerase chain reaction (PCR) test within 7 days
prior to enrollment.
13. Had at least one dose of a COVID-19 vaccine approved or authorized for emergency use
by the FDA.
14. Intrathecal chemotherapy for central nervous system prophylaxis can only be given at
the discretion of the primary oncologist.
a. Note: patients who received high-dose methotrexate are not eligible for the
study.
15. For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive methods, and agree to refrain from donating sperm,
as defined below:
1. With a female partner of childbearing potential or pregnant female partners,
male participants must remain abstinent or use a condom plus an additional
contraceptive method that together result in a failure rate of <1% per year
during the treatment period and for 6 months after the final dose of
Mosun-Pola-SD-CHP. Male participants must refrain from donating sperm during
this same period.
2. 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
individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of
contraception. If required per local guidelines or regulations, locally
recognized adequate methods of contraception and information about the
reliability of abstinence will be described in the Informed Consent Form.
16. Ability to understand a written informed consent document, and the willingness to
sign it.
17. In the opinion of the enrolling investigator, subject must be deemed able to comply
with the study intervention.
Exclusion Criteria:
1. Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy.
2. Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form
of Charcot-Marie-Tooth disease.
3. Prior allogeneic or autologous stem cell transplant.
4. Prior solid organ transplant.
5. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
6. Known or suspected chronic active Epstein-Barr Virus (EBV) infection.
7. History of progressive multifocal leukoencephalopathy (PML).
8. Current or within 6 months of central nervous system (CNS) disease, such as stroke,
epilepsy, CNS vasculitis, or neurodegenerative disease.
9. Patients with SARS-CoV-2 antigen or PCR testing positivity within 30 days prior to
Cycle 1 Day 1.
a. Any patient with documented SARS-CoV-2 infection within 6 months prior to planned
Cycle 1 Day 1 must have no persistent respiratory symptoms, no evidence of residual
sequelae, and have a negative PCR test for SARS-CoV-2.
10. Administration of a live, attenuated vaccine within 4 weeks before start of study
therapy or anticipation that such a live, attenuated vaccine will be required during
the study.
11. On immunosuppressant therapy for an active autoimmune disease, including, but not
limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune
hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel
disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener
granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis.
a. Exceptions may be made for patients with a remote history of or well-controlled
autoimmune disease, excluding patients on systemic immunosuppression for autoimmune
disease, or patients who received such immunosuppression within 1 year prior.
12. Clinically significant history of liver disease, including viral or other hepatitis,
current alcohol abuse, or cirrhosis.
13. Recent major surgery within 4 weeks before the start of C1D1 with the exception of
lymph node biopsies for diagnosis.
14. Prior treatment with radiotherapy within 2 weeks prior to Cycle 1 Day 1.
1. If patients have received radiotherapy within 4 weeks prior to the initiation
of study treatment, patients must have at least one measurable lesion outside
of the radiation field to be eligible.
2. Patients who have only one measurable lesion that was previously irradiated but
subsequently progressed are eligible.
15. History of previous anthracycline exposure.
16. CNS or meningeal involvement at diagnosis.
17. Richter's Transformation (e.g., DLBCL transformed from an underlying chronic
lymphocytic leukemia (CLL) ).
18. Patients with primary mediastinal large B cell lymphoma (PMBCL).
19. Creatinine clearance <40 mL/min by Cockcroft-Gault.
20. Poor hepatic function, defined as total bilirubin concentration greater than 3.0
mg/dL or transaminases over 4 times the maximum normal concentration, unless these
abnormalities are felt to be related to the lymphoma (which should be explicitly
documented by the enrolling physician).
21. Pulmonary dysfunction, defined as receiving supplemental O2 or significant pulmonary
comorbidities (e.g., history of pneumonitis, severe chronic obstructive pulmonary
disease (COPD) ).
22. Significant cardiovascular disease (e.g., New York Heart Association Class III or IV
cardiac disease, congestive heart failure, myocardial infarction within the previous
6 months, unstable arrhythmias, or unstable angina) or significant pulmonary
disease.
23. Active infectious disease (if patient is on medications for such situations,
enrolling physician should explicitly document justification of meeting this
criteria).
24. Known concurrent bone marrow malignancies (e.g., myelodysplastic syndrome) or poor
bone-marrow reserve, defined as neutrophil count less than 1.5 × 10^9/L or platelet
count less than 100 × 10^9/L, unless caused by bone-marrow infiltration with
lymphoma.
25. History of a second concurrent active malignancy or prior malignancy which required
chemotherapy treatment within the preceding 2 years (other than cured basal or
squamous cell carcinoma, low-risk prostate cancer on observation, and other in situ
carcinomas that were completely treated).
26. Treatment with any investigational drug within 30 days before enrollment.
27. Unable or unwilling to sign consent.
Gender:
All
Minimum age:
70 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Froedtert Hospital & the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Contact:
Last name:
Nirav Shah, MD
Phone:
414-805-4600
Email:
nshah@mcw.edu
Start date:
December 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Medical College of Wisconsin
Agency class:
Other
Source:
Medical College of Wisconsin
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06594939
