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DALY 2.0 USA/ MB-CART2019.1 for DLBCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04792489
Recruitment Status : Recruiting
First Posted : March 11, 2021
Last Update Posted : July 14, 2021
Sponsor:
Information provided by (Responsible Party):
Miltenyi Biomedicine GmbH

Brief 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.

Condition or disease Intervention/treatment Phase
DLBCL Biological: MB-CART2019.1 Phase 2

Detailed 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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center Single Arm Phase II Study to Evaluate the Safety and Efficacy of Genetically Engineered Autologous Cells Expressing Anti-CD20 and Anti-CD19 Specific Chimeric Antigen Receptor in Subjects With Relapsed and/or Refractory Diffuse Large B Cell Lymphoma
Actual Study Start Date : May 25, 2021
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : April 30, 2024


Arm Intervention/treatment
Experimental: Single, open label Biological: MB-CART2019.1
Chimeric antigen receptor (CAR) T cell therapy




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 1 month ]
    ORR


Secondary Outcome Measures :
  1. Complete Response Rate [ Time Frame: 6 months ]
    CRR

  2. Duration of Response [ Time Frame: Up to 2 years ]
    DOR

  3. Overall Response Rate [ Time Frame: 6 months ]
    ORR

  4. Best Overall Response [ Time Frame: 2 years ]
    BOR

  5. Progression Free Survival [ Time Frame: Up to 2 years ]
    PFS

  6. Overall Survival [ Time Frame: Up to 2 years ]
    OS

  7. Pharmacokinetics of MB-CART2019.1 [Maximum concentration (Cmax)] [ Time Frame: Up to 2 years ]
    Bioanalytical

  8. Pharmacokinetics of MB-CART2019.1 [Time to maximum concentration (Tmax)] [ Time Frame: Up to 2 years ]
    Bioanalytical

  9. Pharmacokinetics of MB-CART2019.1 [Area under the curve (AUC)] [ Time Frame: Up to 2 years ]
    Bioanalytical


Other Outcome Measures:
  1. Pharmacodynamics [Levels of cytokines in blood] [ Time Frame: Up to 2 years ]
    Bioanalytical

  2. Correlation of tumor CD19 and CD20 antigen expression with disease progression and relapse [ Time Frame: Up to 2 years ]
    Bioanalytical

  3. Quality of Life (QoL) assessments [EQ-5D-5L] [ Time Frame: Up to 2 years ]
    Health Outcomes

  4. Patient-Reported Outcome (PRO) assessment [FACT-Lym] [ Time Frame: Up to 2 years ]
    Health Outcomes



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04792489


Contacts
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Contact: Remi Kaleta +1 (339) 221-6213 remik@miltenyi.com
Contact: Anna Wijatyk Anna.Wijatyk@miltenyi.com

Locations
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United States, Arizona
Banner MD Anderson Cancer Center Active, not recruiting
Gilbert, Arizona, United States, 85234
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Sharan Claire         
United States, Connecticut
Yale University Active, not recruiting
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Julia Jones         
United States, Michigan
University of Michigan Active, not recruiting
Ann Arbor, Michigan, United States, 48109
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Sharon Yim         
Sponsors and Collaborators
Miltenyi Biomedicine GmbH
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Responsible Party: Miltenyi Biomedicine GmbH
ClinicalTrials.gov Identifier: NCT04792489    
Other Study ID Numbers: M-2018-344
First Posted: March 11, 2021    Key Record Dates
Last Update Posted: July 14, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Miltenyi Biomedicine GmbH:
Chimeric antigen receptor
CAR T
CD19
CD20