- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03893019
MB-CART20.1 Melanoma
September 20, 2021 updated by: Miltenyi Biomedicine GmbH
Multicenter Phase I Trial of MB-CART20.1 for the Treatment of Patients With Metastatic Melanoma
This is a phase l multi-centric, single arm, prospective, open, dose-escalation study in patients with unresectable stage III oder IV melanoma.
The trial will include 15 adult patients.
The trial is a classic 3+3 design with 1 Log dose increments and maximum 3 dose levels of the intravenously administered MB-CART20.1.
Study Overview
Detailed Description
This Phase I trial will be the first trial with CD20 CAR transduced T cells in Europe targeting melanoma.
The rationale for the trial is based on the finding that melanoma cancer sustaining cells express CD20 and that targeting CD20+ cells in preclinical model has a strong antitumor effect.
Study Type
Interventional
Enrollment (Anticipated)
15
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Christine Schubert
- Phone Number: +49 2204 8306 6564
- Email: christines@miltenyibiotec.de
Study Contact Backup
- Name: Sandra Karitzky, Dr.
- Phone Number: +49 2204 8306 6560
- Email: sandrak@miltenyibiotec.de
Study Locations
-
-
NRW
-
Cologne, NRW, Germany, 50937
- Recruiting
- University Hospital of Cologne - Clinic for Internal Medicine I
-
Contact:
- Peter Borchmann, Prof. Dr.
- Phone Number: 88159 +49 221 478
- Email: peter.borchmann@uk-koeln.de
-
Contact:
- Udo Holtick, PD Dr.
- Phone Number: +49 221 478 4407
- Email: udo.holtick@uk-koeln.de
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Male or female patients with
- Histologically confirmed unresectable stage III or stage IV melanoma
- Willingness to provide a tumor biopsy between the screening visit and prior to administration of the IMP and eight weeks after treatment
- Progressive disease despite treatment with indicated standard therapies. Time window for decision about progressive disease is to be made depending on the treatment regimen chosen.
- Measurable lesions according to RECIST1.1
- ECOG (Eastern cooperative oncology group) performance status of 0-2
- Negative serological hepatitis B (HBV) test defined as negative tests for HBsAg and HBcAb, unless serology is positive due to recent IVIG therapy, HBcAb positivity will be allowed if HbsAb is present, negative testing of HCVAb, negative human immunodeficiency virus (HIV) 1/2 test within 6 weeks prior to enrollment.
- Estimated life expectancy of more than 6 months
- At least 18 years of age
- WBC ≥ 2500/µL
- ANC ≥ 1000/µL
- Platelets ≥ 75 x 103/µL
- Hemoglobin ≥ 9 g/dL
- AST ≤ 3 x upper limit of normal (ULN) for patients without liver metastasis
- AST < 5 x ULN for patients with liver metastasis
- Total Bilirubin ≤ 2 x ULN
- patients with Gilbert's Syndrome increase of indirect bilirubin < 6mg/dL
- No childbearing potential (i.e. postmenopausal, absence of menstrual bleeding for at least 1 year, hysterectomy, bilateral ovariectomy or tubal section/ligation) or negative pregnancy test at screening and before chemotherapy in women with childbearing potential. Sexually active female patients of childbearing potential should use one of the following highly effective methods of contraception (Pearl index < 1%): hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine devices or systems (e.g. hormonal and non-hormonal IUD), or vasectomized sexual partner for at least 1 month before the trial start, during the course of the trial and in the 6 months following dosing. Sexual abstinence is restricted to true abstinence ( in line with the preferred and usual lifestyle of the subject).
- male patients, unless surgically sterile, must be using two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child throughout the trial and for up to 12 months after dosing.
- Signed and dated informed consent before conduct of any trial-specific procedure.
Exclusion Criteria:
- Any evidence of brain metastases
- CNS (central nervous system) disorders and previous strokes, if clinically relevant
- Patients with epilepsy
- Clinically relevant autoimmune disorders or history of clinically relevant autoimmune disorders
- Patients with T-cell lymphoma
- Treatment with anti-CD20 antibodies or checkpoint blockade inhibitors within 6 weeks before leukapheresis
- Chemotherapy within 6 weeks prior to leukapheresis
- History of primary immunodeficiency
- Creatinine clearance < 50 ml/min calculated according to the modified formula of Cockcroft and Gault
- concurrent systemic radiotherapy
- Use of systemic corticosteroids and immunosuppressive medication except prednisone ≤ 10 mg QD or equivalent
- Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris)
- Other investigational treatment within 4 weeks before MB-CART20.1 infusion
- 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 related toxicities
- Patients in which such medication (likely to be given during trial participation) is contraindicated for other reasons than hypersensitivity, e.g. live vaccines and fludarabine.
- Severe pulmonary disease (DLCO and/or FEV1 < 65%, dyspnoea at rest)
- Active systemic fungal, viral or bacterial infection
- Pregnant or lactating women
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1: 1x10e5 MB-CART20.1 cells
3+3 patients will be treated with 1x10e5 MB-CART20.1 cells per kg body weight administered intravenously
|
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells targeting CD20.positive tumor cells
Other Names:
|
Experimental: Dose Level 2: 1x10e6 MB-CART20.1 cells
3+3 patients will be treated with 1x10e6 MB-CART20.1 cells per kg body weight administered intravenously
|
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells targeting CD20.positive tumor cells
Other Names:
|
Experimental: Dose Level 3: 1x10e7 MB-CART20.1 cells
3+3 patients will be treated with 1x10e7 MB-CART20.1 cells per kg body weight administered intravenously
|
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells targeting CD20.positive tumor cells
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determination of MTD
Time Frame: Week 4 after infusion of MB-CART20.1
|
MTD is defined as the highest dose level at which < 33% of patients experience dose limiting toxicity (DLT)
|
Week 4 after infusion of MB-CART20.1
|
Safety and Toxicity Assessment per Adverse Event reporting classified according to CTCAE V5.0
Time Frame: until day 28 after infusion of MB-CART20.1
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per Adverse Event reporting classified according to CTCAE V5.0
|
until day 28 after infusion of MB-CART20.1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Response
Time Frame: 1 year after infusion of MB-CART20.1
|
Number of patients with either Complete Response, Partial Response, Stable Disease or Progressive Disease using RECIST 1.1
|
1 year after infusion of MB-CART20.1
|
Frequency 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
|
1 year after infusion of MB-CART20.1
|
Phenotype and Persistence of infused MB-CART20.1
Time Frame: 1 year after infusion of MB-CART20.1
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Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.
|
1 year after infusion of MB-CART20.1
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Presence and phenotype of MB-CART20.1 and B cells in biopsies
Time Frame: Screening, 8 weeks after infusion of MB-CART20.1
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Tumor biopsies for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed
|
Screening, 8 weeks after infusion of MB-CART20.1
|
Number of CD20+ tumor cells
Time Frame: Screening, 8 weeks after infusion of MB-CART20.1
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Tumor biopsies for determination of number of CD20+ tumor cells
|
Screening, 8 weeks after infusion of MB-CART20.1
|
Persistence of T-cell expansion for each dose group
Time Frame: Day 0 and week 12
|
Blood samples for determination MB-CART20.1 levels (transgene copies / genomic DNA)
|
Day 0 and week 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Peter Borchmann, Prof., Universitätsklinikum Köln
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 8, 2019
Primary Completion (Anticipated)
July 1, 2022
Study Completion (Anticipated)
July 1, 2022
Study Registration Dates
First Submitted
March 6, 2019
First Submitted That Met QC Criteria
March 25, 2019
First Posted (Actual)
March 27, 2019
Study Record Updates
Last Update Posted (Actual)
September 21, 2021
Last Update Submitted That Met QC Criteria
September 20, 2021
Last Verified
September 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- M-2015-307
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma (Skin)
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Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
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Roswell Park Cancer InstituteNational Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
-
National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
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William CarsonSchering-PloughCompletedStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
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Roswell Park Cancer InstituteCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IB Skin MelanomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin MelanomaUnited States
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Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
-
National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IIIA Skin MelanomaUnited States, Australia
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIIA Skin MelanomaUnited States
Clinical Trials on MB-CART20.1
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Miltenyi Biomedicine GmbHActive, not recruitingNon-Hodgkin's Lymphoma | Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma | B-cell Lymphoma Refractory | B-cell Lymphoma RecurrentGermany
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University of ThessalyCompletedBody Composition | Physical Fitness | Energy Expenditure | Resting Metabolic RateGreece
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Ceragem Clinical Inc.Not yet recruitingKyphosis | Cervical Kyphosis | Cervical Lordosis
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Mustang BioNational Cancer Institute (NCI)RecruitingMantle Cell Lymphoma Recurrent | Mantle Cell Lymphoma Refractory | Small Lymphocytic Lymphoma, Relapsed | Waldenstrom's Macroglobulinemia Recurrent | Follicular B-cell Non-Hodgkin's Lymphoma | B-cell Lymphoma Refractory | Waldenstrom's Macroglobulinemia Refractory | Chronic Lymphoid Leukemia in RelapseUnited States
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Microbio Co LtdCompletedColorectal CancerTaiwan
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Mage BiologicsAlimentiv Inc.RecruitingUlcerative ColitisAustralia
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Biotech DentalRecruitingDental Implant | Dental Restoration | Dentistry | Implant-supported Fixed ProsthesisFrance
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York UniversityCentre for Addiction and Mental HealthSuspendedDisorder, Major DepressiveCanada
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Mustang BioEnrolling by invitationDiffuse Large B Cell Lymphoma | Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) | Hairy Cell Leukemia | Mantle Cell Lymphoma Recurrent | Mantle Cell Lymphoma Refractory | Chronic Lymphocytic Leukemia in Relapse | Small Lymphocytic Lymphoma, Relapsed | Waldenstrom's Macroglobulinemia Recurrent | Follicular B-cell Non-Hodgkin's Lymphoma and other conditionsUnited States