DALY 2.0 USA/ MB-CART2019.1 for DLBCL
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
M-2018-344 (primary)
NCI-2021-08357
Summary
This is an open label, single arm, phase II study to determine the efficacy, safety and PK
(persistence) of MBCART2019.1 cells in adults with relapsed or refractory DLBCL after
receiving at least two lines of therapy.
Objectives
A prospective, single arm, open label, multi-center, phase II study of autologous T cells
engineered against both CD19 and CD20 antigens for subjects with relapsed or refractory DLBCL
after receiving at least two lines of therapy. The investigational agent is the MB-CART2019.1
cells. After successful screening, subjects will undergo leukapheresis to collect product for
manufacturing. In preparation for the fresh product infusion, subjects will undergo a
lymphodepleting regimen with cyclophosphamide and fludarabine, or bendamustine. Cell infusion
will be administered intravenously at a dose of 2.5 x 106 CAR+ cells/kg body weight. The
study will start with enrollment of 3 subjects in the lead-in safety phase, and after safety
is evaluated, the study will continue with enrollment of the remaining subjects. Subjects
will be followed for up to 2 years, for efficacy and safety outcomes as well as
health-related quality of life (HRQol). Additional long-term follow-up will be conducted for
participants under a separate long-term follow-up protocol.
Eligibility
- Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
- CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)
- Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT
- Chemotherapy-refractory disease is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
- Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen
- CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) first-line therapy.
- CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least 1 prior line of systemic therapy
- Age =18 years
- Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL
- Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014) for DLBCL and SCNSL while IPCG criteria for the primary PCNSL.
- Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses
- No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)
- If the subject has history of CNS disease (not applicable to CNS cohort), then he/she must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs)
- If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable.
- A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) > 60mL/min
- Cardiac ejection fraction (EF) = 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
- Resting O2 saturation >90% on room air
- Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 times the Upper Limit of Normal (ULN) for age
- Total bilirubin <1.5 mg/dl, except in individuals with Gilbert's syndrome
- Absolute neutrophil count (ANC) > 1000/µL
- Absolute lymphocyte count > 100/µL
- Platelet count > 50,000/µL
- Estimated life expectancy of more than 3 months other than primary disease
Treatment Sites in Georgia
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