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Trial record 1 of 1 for:    M-2016-312 | NHL | Germany
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MB-CART20.1 Lymphoma

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ClinicalTrials.gov Identifier: NCT03664635
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Miltenyi Biomedicine GmbH

Study Description
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Brief Summary:
This trial is a phase I/II trial to assess safety, dose finding and feasibility of ex vivo generated MB-CART20.1 cells in patients with relapsed or refractory CD20 positive B-NHL.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma Non-Hodgkin's Lymphoma B-cell Lymphoma Refractory B-cell Lymphoma Recurrent Biological: MB-CART20.1 Phase 1 Phase 2

Detailed Description:
MB-CART20.1 consists of autologous Anti-CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in Non-Hodgkin-Lymphoma (NHL)
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients With Relapsed or Resistant CD20 Positive B-NHL
Actual Study Start Date : September 25, 2018
Estimated Primary Completion Date : February 10, 2022
Estimated Study Completion Date : November 10, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase I - Safety Dose Level
In phase I three (3) + 3 patients will be treated with 1x10^5 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the preceding safety dose level
 Biological: MB-CART20.1
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in NHL
Other Names:
  • CD20-targeting CAR T Cells
  • Anti-CD20 CAR T cells
Experimental: Phase I - Dose Level 1
In phase I six (6) + 3 patients will be treated with 1x10^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 1
 Biological: MB-CART20.1
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in NHL
Other Names:
  • CD20-targeting CAR T Cells
  • Anti-CD20 CAR T cells
Experimental: Phase I - Dose Level 2
In phase I six (6) + 3 patients will be treated with 3x10^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 2
 Biological: MB-CART20.1
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in NHL
Other Names:
  • CD20-targeting CAR T Cells
  • Anti-CD20 CAR T cells
Experimental: Phase II
The number of additional patients who will be treated with MB-CART20.1 cells in Phase II is depending on the number of evaluable patients treated with the maximum tolerated dose (MTD) level and the results in Part I
 Biological: MB-CART20.1
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in NHL
Other Names:
  • CD20-targeting CAR T Cells
  • Anti-CD20 CAR T cells


Outcome Measures
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Primary Outcome Measures :
  1. Phase I - Determination of the maximum tolerated dose (MTD) [ Time Frame: until day 28 after infusion of MB-CART20.1 ]
    MTD is defined as the highest dose level at which < 33% of patients experience Dose Limiting Toxicity (DLT). Safety and toxicity assessment of MB-CART20.1 per adverse events (AE) reporting classified according to CTCAE version 5.0.

  2. Phase II - Best overall response rate [ Time Frame: 3 months after infusion of MB-CART20.1 ]
    Response (Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD)) is defined according to Cheson criteria.


Secondary Outcome Measures :
  1. Phase I - Related safety and toxicity of MB-CART20.1 [ Time Frame: months 3, 6, 9 and 12 after infusion of MB-CART20.1 ]
    Per adverse events (AE) reporting classified according to CTCAE version 5.0.

  2. Phase I - Best overall response rate over 4 weeks and 3 months [ Time Frame: 4 weeks and 3 months after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  3. Phase I - Best overall response rate over 1 year [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  4. Phase I - Occurrence of B-cell aplasia [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.

  5. Phase I - Phenotype and Persistence of MB-CART20.1 [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.

  6. Phase II - Best overall response rate over 1 year [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  7. Phase II - Overall response rate over 4 weeks and 3 months [ Time Frame: 4 weeks and 3 months after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  8. Phase II - Overall response rate over 1 year [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  9. Phase II - Number of patients with CR, PR, SD and PD [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  10. Phase II -Percentage of patients with CR, PR, SD and PD [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Response (CR, PR, SD and PD) is defined according to Cheson criteria.

  11. Phase II - Safety and toxicity assessment of MB-CART20.1 [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Per adverse events (AE) reporting classified according to CTCAE version 5.0.

  12. Phase II - Occurrence of B-cell aplasia [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.

  13. Phase II - Phenotype and Persistence of MB-CART20.1 [ Time Frame: 1 year after infusion of MB-CART20.1 ]
    Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.


Eligibility Criteria
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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:

  • Refractory/relapsed CD20+ B-NHL (including malignant transformation like Richter's transformation) with no curative treatment option.
  • At least 18 years of age
  • Estimated life expectancy of more than 3 months
  • ECOG performance status (Eastern cooperative oncology group) of 0-2
  • Negative serological HBV (Hepatitis B virus) test, negative testing of HCVAb (Hepatitis C virus Antibody), negative HIV1/2 (Human immunodeficiency virus 1/2 ) test within 6 weeks prior to enrollment
  • No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential.
  • Signed and dated informed consent before conduct of any trial-specific procedure

Exclusion Criteria:

  • Participation in another interventional trial that could interact with this trial
  • Any evidence 0f CNS (Central nervous system) involvement
  • Known history or presence of clinically relevant CNS pathology
  • Patients with history of primary immunodeficiency,
  • Patients with any history of auto-immune induced condition such as those caused by checkpoint inhibitors, MEK inhibitors or BRAF inhibitors, for example pituitary hypophysitis must be excluded
  • Patients with Chronic Lymphocytic Leukemia unless suffering from malignant transformation
  • Active systemic fungal, viral or bacterial infection
  • Serious cardiac functional incapacity (class III or IV as defined by the New York Heart Association Classification)
  • Severe pulmonary disease (DLCO (Transfer factor of the lung for carbon monoxide) and/or FEV1 (Forced expiratory volume in 1 second) < 65%, dyspnea at rest)
  • Liver dysfunction as indicated by a total bilirubin, AST (Aspartate Aminotransferase), and ALT (Alanine aminotransferase) ≥ 2 the institutional ULN (Upper limit of normal) value, unless directly attributable to the patient's tumor
  • Creatinine clearance <50 ml/min calculated according to the modified formula of Cockcroft and Gault
  • Pregnant or lactating women
  • Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before enrollment.
  • Medical condition requiring prolonged use of systemic corticosteroids (> 1 month)
  • Prior therapy with genetically modified substances
  • Use of anti-CD20 antibodies within 4 weeks before leukapheresis
  • Chemotherapy within 4 weeks prior to leukapheresis
  • Other treatment within 4 weeks or two half-lives, whichever is longer before MB-CART20.1 infusion. This pertains to immunomodulatory therapies such as checkpoint inhibitors because of the influence on the immune system
  • Concurrent systemic radiotherapy
  • Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment of related toxicities
  • Patients in which such medication is contraindicated for other reasons than hypersensitivity (e.g. live vaccines and fludarabine)
  • Patients in which trial related procedures are contraindicated as judged by the investigator, e.g. lumbar punctures for CSF (Cerebrospinal fluid) sampling
  • Patient's lack of accountability, inability to appreciate the nature, meaning and consequence of the trial and to formulate his/her own wishes correspondingly
  • Patients who have a relationship of dependence or employer employee relationship to the sponsor or the investigator
  • Committal to an institution on judicial or official order
  • Cerebral dysfunction, legal incapacity
  • Other investigational treatment within 4 weeks before IMP (Investigational Medicinal Product) infusion
  • Clinically relevant autoimmune diseases or history of autoimmune disease
Contacts and Locations
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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): NCT03664635


Contacts
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Contact: Christine Schubert +49 2204 8306 6564 christines@miltenyibiotec.de
Contact: Sandra Karitzky, Dr. +49 2204 8306 6560 sandrak@miltenyibiotec.de

Locations
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Germany
University Hospital of Cologne - Clinic for Internal Medicine I Recruiting
Cologne, Germany, 50937
Contact: Peter Borchmann, Prof. Dr.    +49 (0) 221 478-88159    peter.borchmann@uni-koeln.de   
Universitätsklikum Leipzig, AöR Not yet recruiting
Leipzig, Germany
Contact: Vladan Vucinic, Dr.    +49 341 97-13141    vladan.vucinic@medizin.uni-leipzig.de   
Contact: Georg-Nikolaus Franke, Dr.       georg-nikolaus.franke@medizin.uni-leipzig.de   
Sponsors and Collaborators
Miltenyi Biomedicine GmbH
Investigators
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Principal Investigator: Peter Borchmann, Prof. Dr. Universitätsklinikum Köln
More Information
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Responsible Party: Miltenyi Biomedicine GmbH
ClinicalTrials.gov Identifier: NCT03664635    
Other Study ID Numbers: M-2016-312
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases