Trial Search Results

DALY 2.0 USA/ MB-CART2019.1 for DLBCL

This is a prospective, single arm, open label, multi-center, Phase IIstudy of autologous T cells engineered against both CD19 and CD20antigens (MB-CART2019.1) for subjects with refractory and/or relapsedDLBCL. Since one of the important mechanisms of relapse for bothtargeted monoclonal antibody treatment and CAR-T therapy has beenshown to be downregulation of the targeted antigen that allows tumorcells to escape destruction (Hiraga et al, 2009; Tedder and Engel,1994; Neelapu et al, 2019) and given the overlap of CD19 and CD20expression on B cells, we postulate that simultaneous targeting ofthese two separate B cell antigens in DLBCL subjects with MBCART2019.1 may result in a more complete B cell ablation and areduced risk of tumor cell escape that may translate into lessrelapse, longer duration of response and significant improvement ofoverall survival.The primary aim of this study is to determine the efficacy of MBCART2019.1 cells administered following a conditioninglymphodepletion regimen as measured by ORR per Lugano 2014criteria(Cheson et al, 2014) at 1 month and duration of response in subjectswith DLBCL who are refractory or have relapsed after failing at leasttwo lines of therapy.In addition, this study will evaluate the safety and potentialclinical activity, CRR, PFS, OS, and impact on QoL/PRO (EQ-5D-5L andFACT-Lym) in all subjects.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Miltenyi Biomedicine GmbH

Stanford Investigator(s):

Intervention(s):

  • Biological: MB-CART2019.1

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Histologically confirmed DLBCL or associated subtype, defined by WHO 2016
   classification

   - 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 being ineligible for or not consenting to ASCT

   - 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)

   - Subject must have at least 10 unstained slides of tissue available prior to
   MBCART2019.1 Infusion. If archival tissue is not available, subject must be willing to
   undergo attempted repeat biopsy

   - No clinical suspicion of CNS lymphoma

   - If the subject has history of CNS disease, then he/she must have no signs or symptoms
   of CNS disease, have no active disease on magnetic resonance imaging (MRI) and 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 must be greater than 12
   months prior to leukapheresis and any neurological deficits must be stable

   - A creatinine clearance > 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 > 1000/μL

   - Absolute lymphocyte count > 100/μL

   - Platelet count > 50,000/μL

   - Estimated life expectancy of more than 3 months other than primary disease

   - Subjects of child-bearing or child-fathering potential must be willing to practice
   birth control from the time of enrollment on this study until the follow-up period of
   the study.

Exclusion Criteria:

   - Primary CNS lymphoma

   - Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL)

   - Unable to give informed consent

   - Known history of infection with human immunodeficiency virus (HIV) or active hepatitis
   B (HBsAg positive), unless confirmed to be polymerase chain reaction (PCR) negative;
   antiviral prophylaxis isrequired if HBsAg negative and anti-HBc positive

   - Known history of infection with hepatitis C virus (anti-HCV positive) unless viral
   load is undetectable per quantitative PCR and/or nucleic acid testing

   - Known history of active seizures or presence of seizure activities or on active,
   anti-seizure medications within the prior 12 months

   - Known history of CVA within prior 12 months.

   - Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic
   neuritis, or other immunologic or inflammatory disease

   - Presence of CNS disorder that, in the judgment of the investigator, may impair the
   ability to evaluate neurotoxicity

   - Active systemic fungal, viral, or bacterial infection

   - Pregnant or breast-feeding woman

   - Previous or concurrent malignancy with the following exceptions:

   - Adequately treated basal cell or squamous cell carcinoma (adequate wound healing
   required prior to study entry)

   - In situ carcinoma of the cervix or breast, treated curatively and without evidence of
   recurrence for at least 2 years prior to the study

   - Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron
   or tamoxifen and in clinical remission of ≥ 2 years

   - A primary malignancy which has been completely resected / treated with curative intent
   and in complete remission of ≥ 2 years

   - History of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid
   arthritis, systemic lupus erythematosus)requiring systemic immunosuppressive or system
   disease modifying agents within the last 2 years

   - Medical condition requiring prolonged use of systemic corticosteroids equivalent to
   prednisone >10 mg/day

   - History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
   other clinically significant cardiac disease within 6 months of enrollment

   - Concurrent radiotherapy (allow up to time of leukapheresis)

   - Baseline dementia that would interfere with therapy or monitoring, determined using
   Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline

   - History of severe immediate hypersensitivity reaction to any of the agents used in
   this study

   - Refusal to participate in additional lentiviral gene therapy LTFU protocol

   - Prior CAR-T therapy for any indication

   - Prior allogeneic stem cell transplant for any indication

   - Prior BITE antibodies for cancer therapy

   - Prior T cell receptor-engineered T cell therapy

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sharan Claire
650-721-4091
Recruiting