Status and phase
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About
This is a two-arm, open-label, phase Ib single-site study with expansion cohorts testing the addition of mosunetuzumab to intensive platinum-based salvage chemotherapy in patients with relapsed/refractory aggressive B cell lymphoma intending to pursue consolidative autoSCT. The hypothesis of this study is that mosunetuzumab can be safely combined with platinum-based salvage chemotherapy in this patient population, and that this approach may outperform chemoimmunotherapy approaches that instead incorporate rituximab retreatment. The enrolling physician's choice of the chemotherapy backbone will determine a patient's assigned study arm (Arm A = DHAX, Arm B = ICE). The two arms will accrue patients to phase Ib and expansion cohorts as well as be analyzed independently.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Diagnosis of diffuse large, high-grade, or transformed B cell lymphoma or follicular lymphoma grade 3B that is refractory to or has relapsed after anti-CD20 mAb plus anthracycline-containing combination chemotherapy. A biopsy immediately prior to enrollment is not mandatory.
Must have received at least one but no more than two prior lines of systemic treatment containing conventional cytotoxic chemotherapy for lymphoma. Conventional cytotoxic chemotherapy with or without an anti-CD20 mAb for prior/underlying indolent NHL (with or without maintenance/extended-use rituximab) will count as one line of systemic therapy.
Planning to undergo autologous stem cell transplantation after platinum-based salvage chemotherapy.
At least 18 years of age.
ECOG performance status ≤ 2
Adequate hematologic function (unless due to underlying lymphoma per the investigator), defined as follows:
Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled if the following criteria are met:
Normal laboratory values:
The effects of mosunetuzumab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (as defined in protocol) prior to study entry, for the duration of study treatment, and for 3 months following the final dose of mosunetuzumab. Specifically, women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for 3 months after the final dose of mosunetuzumab as applicable. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol with a female partner of childbearing potential or pregnant female partner must also agree to use adequate contraception prior to the study, for the duration of study treatment, and for 3 months following the final dose of mosunetuzumab.
Ability to understand and willingness to sign an IRB approved written informed consent document.
Exclusion criteria
Note: The use of inhaled corticosteroids, mineralocorticoids for management of orthostatic hypotension, and single dose dexamethasone for nausea or B symptoms is permitted.
History of solid organ transplantation.
History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies (mAbs).
Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab formulation, including mannitol.
History of erythema multiforme, grade ≥ 3 rash, or blistering following prior treatment with immunomodulatory derivatives.
Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 1 week of Day 1 of Cycle 1.
Known or suspected chronic active Epstein-Barr virus (EBV) infection.
Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis.
Active hepatitis B infection:
*Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation.
Active hepatitis C infection:
*Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation.
Known history of human immunodeficiency virus (HIV) positive status.
History of progressive multifocal leukoencephalopathy (PML).
Administration of 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:
Patients must not receive live, attenuated vaccines (e.g., FluMist®) while receiving study treatment or after the last dose until B cell recovery to the normal ranges.
Other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following:
Active autoimmune disease requiring treatment.
History of autoimmune disease, including, but not limited to, myocarditis, interstitial lung disease (idiopathic, autoimmune, or drug-induced), pneumonitis (autoimmune or drug-induced), myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis:
Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, 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) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm).
Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day 1 or anticipation of a major surgical procedure during the study.
Pregnant or lactating or intending to become pregnant during the study:
*Women of childbearing potential must have one negative serum pregnancy test result (minimum sensitivity, 25 mIU/mL) within seven days of Cycle 1 Day 1.
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.
Primary purpose
Allocation
Interventional model
Masking
40 participants in 2 patient groups
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Central trial contact
Nancy L Bartlett, M.D.
Data sourced from clinicaltrials.gov
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