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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 Biotec GmbH

Tracking Information
First Submitted Date  ICMJE September 3, 2018
First Posted Date  ICMJE September 10, 2018
Last Update Posted Date March 8, 2019
Actual Study Start Date  ICMJE September 25, 2018
Estimated Primary Completion Date February 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03664635 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MB-CART20.1 Lymphoma
Official Title  ICMJE A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients With Relapsed or Resistant CD20 Positive B-NHL
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • B-cell Lymphoma Refractory
  • B-cell Lymphoma Recurrent
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Biological: MB-CART20.1
  • 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
    Intervention: Biological: MB-CART20.1
  • 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
    Intervention: Biological: MB-CART20.1
  • 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
    Intervention: Biological: MB-CART20.1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2018)
19
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 10, 2022
Estimated Primary Completion Date February 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christine Schubert +49 2204 8306 6564 christines@miltenyibiotec.de
Contact: Sandra Karitzky, Dr. +49 2204 8306 6560 sandrak@miltenyibiotec.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03664635
Other Study ID Numbers  ICMJE M-2016-312
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Miltenyi Biotec GmbH
Study Sponsor  ICMJE Miltenyi Biotec GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Borchmann, Prof. Dr. Universitätsklinikum Köln
PRS Account Miltenyi Biotec GmbH
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP