Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Keywords
Diffuse large B-cell lymphoma, Mosunetuzumab, circulating tumor DNA, Measurable residual disease, Geriatric assessment
Brief summary
Older patients with diffuse large B- cell lymphoma (DLBCL) do not have the same rates of disease control as younger patients and are at risk for toxicity. Identifying which patients might benefit from more therapy at the end of first-line treatment is important. The ability to measure small amounts of persistent lymphoma (circulating tumor DNA or ctDNA) might allow the investigators to risk stratify patients. If older patients have detectable ctDNA in the blood at the end of six cycles of polatuzumab vedotin, rituximab and dose-attentuated CHP chemotherapy, patients will receive a bispecific antibody called mosunetuzumab. The investigators hypothesize this will result in clearing the ctDNA from the blood and result in better disease control and outcomes for patients. The study will also measure the safety of this regimen and the impact on the function of these older patients utilizing a tool called the geriatric assessment.
Interventions
DRUGMosunetuzumab
Mosunetuzumab consolidation therapy will consist of 6 cycles of IV mosunetuzumab at the standard ramp-up dosing (Day 1 1mg, Day 8 2mg, D15 60mg, C2D1 60mg, and 30mg on day 1 of the subsequent 21-day cycles)
DEVICEClonoSEQ
Patients with detectable ClonoSEQ at C6D1 who have a PET/CT that shows a CR will receive mosunetuzumab
Sponsors
Genentech, Inc.
Adaptive Biotechnologies
Lymphoma Research Foundation
Danielle Wallace
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single center, open-label, single arm, phase II pilot study
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged greater than or equal to 70 years of age who are ineligible for full-intensity chemoimmunotherapy at the discretion of the treating investigator. If between the ages of 70-79, the reason for ineligibility should be documented in a clinical note. If 80 or older, the reason for dose-attenuated chemoimmunotherapy is assumed to be age. 2. ECOG performance status of 0-2. 3. Histologically-confirmed DLBCL, NOS, high grade B-cell lymphoma with MYC and BCL2 rearrangements, high grade B-cell lymphoma, NOS, and grade 3b follicular lymphoma 4. Histologic transformation (HT) will be included on the study. This must be confirmed with a biopsy. Patients with HT may have received prior treatment for indolent lymphoma including chemoimmunotherapy but must not have received an anthracycline-containing regimen in the past. 5. Composite and discordant lymphomas containing both indolent and large cell features will be included. 6. Has received no prior therapy for aggressive B-cell lymphoma or HT with the following exceptions: a course of corticosteroids given for lymphoma related symptoms or one cycle of anthracycline containing chemotherapy prior to enrollment on the clinical trial. Pre-phase treatment with polatuzumab vedotin and steroids is allowable at the treating investigator's discretion. 7. Ejection fraction of ≥ 45% on echocardiogram or MUGA 8. Patient has a platelet count of ≥75,000/µL within the screening period unless inadequate function is due to bone marrow infiltration with aggressive B-cell lymphoma in which case the platelet count should be ≥ 30,000/µL 9. Patient has an absolute neutrophil count of ≥1,500/ µL within the screening period unless inadequate function is due to bone marrow infiltration with aggressive B-cell lymphoma in which case the neutrophil count should be ≥500/ µL 10. Patient has a calculated or measured creatinine clearance of \>40 mL/minute within the screening period. 11. Total bilirubin must be less than 1.5 times the upper limit of normal (ULN) unless the elevation is known to be due to Gilbert syndrome or hepatic involvement with aggressive B-cell lymphoma in which case it can be ≤ 3.0 times the ULN. ALT or AST must be ≤ 2.5 times the ULN. 12. Patient has, with treatment in the opinion of the treating investigator, a life expectancy of at least 12 weeks. 13. Signed Informed Consent Form 14. Ability to comply with the study protocol
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ctDNA clearance rate after mosunetuzumab treatment | From the beginning to the end of mosunetuzumab treatment at 18 weeks | The primary endpoint of the trial is the ctDNA clearance rate after mosunetuzumab treatment among the subset of patients in a PET/CT CR but with ctDNA+ at the end of 6 cycles of R-pola-mini-CHP. The rate will be calculated as the number of subjects ctDNA- after mosunetuzumab treatment among all patients treated with mosunetuzumab as part of the Fleming two-stage design. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate and complete response rate of pola-R-mini-CHP | From enrollment to the end of pola-R-mini-CHP treatment at 18 weeks | Objective response rate is the number of patients in the study population who achieve a complete or partial response to therapy, the complete response rate is only those patients who achieve a complete response. |
Countries
United States
Contacts
Primary ContactDanielle Wallace, MD
Backup ContactClinical Trials Office
Outcome results
None listed