A prospective multicenter phase 2 study of the chemotherapy-light combination of intravenous rituximab with the antibody-drug conjugate polatuzumab vedotin and the bispecific antibody glofitamab in previously untreated aggressive B-cell lymphoma patients above 60 years of age ineligible for a fully dose R-CHOP
- Conditions
- aggressive large B-cell lymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-003398-51-AT
- Lead Sponsor
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 125
(1) Patient has provided written informed consent and is able and willing to comply with the study protocol and protocol mandated hospitalizations according to ICH and local regulations.
(2) Patient is above 60 years of age
(3) Patient is not eligible for a fully dosed R-CHOP
(4) Patient has histologically confirmed aggressive B-cell lymphoma.
Note: transformed follicular lymphoma and composite B-cell lymphoma can be included as long as the low-grade component had not obtained systemic treatment.
(5) Patient has at least one measurable FDG PET-positive lymphoma manifestation; defined as lesional maximum FDG uptake higher than the maximum FDG uptake in unaffected liver parenchyma as measured in a reference volume-of-interest with >10 mL
(6) Baseline biopsy material is available for central review.
(7) Female patients considered as women of childbearing potential (WOCBP, see section 5.2.7 for definition) and male patients with female partners considered as WOCPB must
a) agree to either remain completely abstinent (refrain from heterosexual intercourse) or to use at least one effective contraceptive methods that results in a failure rate of < 1% per year from screening until:
o At least 4 months after last dose of glofitamab, 9 months after last dose of polatuzumab vedotin, 12 months after last dose of rituximab or 18 months after last dose of obinutuzumab, whichever is longer, if the patient is female
o At least 4 months after last dose of rituximab, obinutuzumab and glofitamab or 6 months after last dose of polatuzumab vedotin, whichever is longer, if the patient is male
b) refrain from donating ova (female patients) or donating sperm (male patients) during the same period as stated in a).
c) in case of male patients with pregnant female partners, remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom to avoid exposing the embryo.
Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile, see section 5.2.7) as well as azoospermic male patients do not require contraception.
(8) Patient did not receive any prior lymphoma therapy.
Note: Except for a corticosteroid prephase or local radiation to low grade lymphoma.
(9)Patient has a ECOG performance status of = 2.
(10) Patient has a life expectancy (in the opinion of the investigator) of at least 12 weeks.
(11) Patient has adequate liver function:
a) Total bilirubin =1.5 x ULN (=3 x ULN in patients with Gilbert’s syndrome).
b) AST (aspartate aminotransferase)/ALT (alanine aminotransferase), ALP (alkaline phosphatase) =3 x ULN.
o Patients with bone marrow or liver involvement: ALP =5 x ULN.
o Patients with documented liver involvement: AST and/or ALT =5 x ULN.
c) Albumin = 2.5 g/dL.
(12) Patient has adequate hematological function:
a) Neutrophil count of =1.5 x 109 cells/L (1,500/µL).
b) Platelet count of =75 x 109 cells/L (75,000/µL).
c) Hemoglobin (Hb) =9.0 g/dL.
Note: Transfusion of RBCs and platelets is allowed to reach the inclusion criteria. In case screening procedures are leading to situations that would exclude the patient from study participation (such as Hb value below entry criteria), the patient may still be enrolled into the trial after consultation with the sponsor.
d) For patients not receiving therapeutic anti-coagulation: INR or aPTT = 1.5 x ULN).
(13) Patient has adequate renal function:
a) Creatinine = 1.5 x ULN, or
b) Creatinine clearance (CrCl) calculated by Cockroft-Gaul
(1) Patient with chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) (including CD20+ ALL), lymphoblastic lymphoma, Richter`s transformation, Burkitt lymphoma.
(2) Patient = 60 years
(3) Patient with known active infection, or reactivation of a latent infection, whether bacterial (e.g., tuberculosis), viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to study enrollment.
(4) Patient with current > Grade 1 peripheral neuropathy.
(5) Patient with history of confirmed progressive multifocal leukoencephalopathy (PML).
(6) Patient with history of leptomeningeal disease.
(7) Patient with current or history of CNS lymphoma.
(8) Patient with current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Exceptions are allowed fot this trial.
(9) Patient with another invasive malignancy in the last 2 years.
(10) Patient with significant or extensive history of cardiovascular disease or significant pulmonary disease.
Note: Congestive heart failure NYHA II patients can be included if they provide an LVEF >40%.
(11) Patient with active or history of autoimmune disease or immune deficiency (see addendum for a comprehensive list of autoimmune diseases and immune deficiencies), with exceptions.
(12) Patient with uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
Note: Patients with indwelling catheters (e.g., PleurX) are allowed.
(13) Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic.
(14) Patient received treatment with any other standard anti-cancer radiotherapy/chemotherapy including investigational therapy (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks or five times the elimination half-life of the product, whichever is longer, prior to study enrollment.
(15) Patient with prior solid organ transplantation.
(16) Patient with prior allogeneic stem cell transplantation.
(17) Patient with prior treatment with targeted therapies within 4 weeks or five half-lives of the drug, whichever is shorter, prior to study enrollment.
(18) Patient with toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to = Grade 1 except for alopecia, endocrinopathy managed with replacement therapy and stable vitiligo.
(19) Patient with any history of immune related = Grade 3 AE except for endocrinopathy managed with replacement therapy.
(20) Patient with ongoing corticosteroid use 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment.
(21) Patient with treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with exceptions.
(22) Patient who received administration of a live, attenuated vaccine within 4 weeks prior to study enrollment infusion or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the last dose of study treatment.
(23) Patient with history of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the trial is to evaluate an estimator of efficacy of the chemotherapy-light combination of glofitimab, polatuzumab vedotin and rituximab in patients with previously untreated aggressive large B-cell lymphoma.;Secondary Objective: The secondary objectives of the trial are designed to i.) further characterize the outcome, ii.) to evaluate the safety and tolerability of the chemotherapy-light combination R-Pola-Glo in patients with previously untreated DLBCL and only for extension cohort iii) to assess feasibility and safety of the R-Pola-Glo regimen in an outpatient setting.;Primary end point(s): 1 year progression-free survival (PFS) rate of the first 80 patients.<br>;Timepoint(s) of evaluation of this end point: Analysis of the primary outcome endpoint and the secondary endpoints will be performed following recruitment of all analyzable patients and with adequate observation time to assess the 1-years PFS rate.<br>
- Secondary Outcome Measures
Name Time Method