Non Hodgkin Lymphoma Clinical Trial

DALY 2.0 USA/ MB-CART2019.1 for DLBCL

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.

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Full Description

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. 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.

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Eligibility Criteria

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 a tumor biopsy sample, per protocol specified slide availability from the most recent relapse available prior to MBCART2019.1 Infusion. If medically not feasible to obtain biopsy from the most recent relapse and for cases when amount of tissue is limited, sponsor should be consulted, to confirm adequacy of sample for study required analyses.
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 (as estimated either by a 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 > 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). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required 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 (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled 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 or systemic gene modifying therapy for DLBCL
Prior allogeneic stem cell transplant for any indication
Prior BITE antibodies for cancer therapy
Prior T cell receptor-engineered T cell therapy

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

65

Study ID:

NCT04792489

Recruitment Status:

Recruiting

Sponsor:

Miltenyi Biomedicine GmbH

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There are 18 Locations for this study

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Banner MD Anderson Cancer Center
Gilbert Arizona, 85234, United States More Info
Erin Nicoson
Contact
Mayo Clinic
Phoenix Arizona, 85054, United States More Info
Allison Rosenthal, DO
Contact
UC San Diego Health
La Jolla California, 92037, United States More Info
Dimitrios Tzachanis, MD
Contact
Stanford University
Stanford California, 94305, United States More Info
Sharan Claire
Contact
Yale University
New Haven Connecticut, 06520, United States More Info
Alexandra Dormal
Contact
Robert H Lurie Cancer Center
Chicago Illinois, 60611, United States More Info
Reem Karmali, MD
Contact
University of Kansas Cancer Center
Westwood Kansas, 66205, United States More Info
Sunil Abhyankar, MD
Contact
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
Baltimore Maryland, 21201, United States More Info
Saurabh Dahiya, MD
Contact
[email protected]
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Julia Jones
Contact
University of Michigan
Ann Arbor Michigan, 48109, United States More Info
Kathleen Lawrence
Contact
Mayo Clinic
Rochester Minnesota, 55905, United States More Info
Patrick Johnston, MD
Contact
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States More Info
Matthew Lunning, MD
Contact
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Miguel-Angel Perales, MD
Contact
Duke University Medical Center - Division of Hematologic Malignancies
Durham North Carolina, 27705, United States More Info
Ahmed Galal, MD
Contact
Oregon Health and Science University Knight Cancer Institute
Portland Oregon, 97239, United States More Info
Richard Maziarz, MD
Contact
University of Pittsburgh - Hillman Cancer Center
Pittsburgh Pennsylvania, 15260, United States More Info
Alison Sehgal, MD
Contact
UT Southwestern Medical Center
Dallas Texas, 75390, United States More Info
Farrukh Awan, MD
Contact
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Sharon Yim
Contact

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

65

Study ID:

NCT04792489

Recruitment Status:

Recruiting

Sponsor:


Miltenyi Biomedicine GmbH

How clear is this clinincal trial information?

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