MB-CART20.1 Lymphoma

A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients With Relapsed or Resistant CD20 Positive B-NHL

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Hodgkin's Lymphoma; Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma; B-cell Lymphoma Refractory; B-cell Lymphoma Recurrent
• Intervention / Treatment: Biological: MB-CART20.1

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: Interventional
• Enrollment (Anticipated): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 50937
    • University Hospital of Cologne - Clinic for Internal Medicine I
  • Leipzig, Germany
    • Universitätsklikum Leipzig, AöR

Participation Criteria

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I - Determination of the maximum tolerated dose (MTD)	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.	until day 28 after infusion of MB-CART20.1
Phase II - Best overall response rate	Response (Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD)) is defined according to Cheson criteria.	3 months after infusion of MB-CART20.1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I - Related safety and toxicity of MB-CART20.1	Per adverse events (AE) reporting classified according to CTCAE version 5.0.	months 3, 6, 9 and 12 after infusion of MB-CART20.1
Phase I - Best overall response rate over 4 weeks and 3 months	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	4 weeks and 3 months after infusion of MB-CART20.1
Phase I - Best overall response rate over 1 year	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	1 year after infusion of MB-CART20.1
Phase I - Occurrence of B-cell aplasia	Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.	1 year after infusion of MB-CART20.1
Phase I - Phenotype and Persistence of MB-CART20.1	Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.	1 year after infusion of MB-CART20.1
Phase II - Best overall response rate over 1 year	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	1 year after infusion of MB-CART20.1
Phase II - Overall response rate over 4 weeks and 3 months	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	4 weeks and 3 months after infusion of MB-CART20.1
Phase II - Overall response rate over 1 year	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	1 year after infusion of MB-CART20.1
Phase II - Number of patients with CR, PR, SD and PD	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	1 year after infusion of MB-CART20.1
Phase II -Percentage of patients with CR, PR, SD and PD	Response (CR, PR, SD and PD) is defined according to Cheson criteria.	1 year after infusion of MB-CART20.1
Phase II - Safety and toxicity assessment of MB-CART20.1	Per adverse events (AE) reporting classified according to CTCAE version 5.0.	1 year after infusion of MB-CART20.1
Phase II - Occurrence of B-cell aplasia	Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.	1 year after infusion of MB-CART20.1
Phase II - Phenotype and Persistence of MB-CART20.1	Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed.	1 year after infusion of MB-CART20.1

Collaborators and Investigators

• Sponsor: Miltenyi Biomedicine GmbH
• Investigators: Principal Investigator: Peter Borchmann, Prof. Dr., Universitatsklinikum Koln

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 25, 2018
• Primary Completion (ANTICIPATED): February 10, 2022
• Study Completion (ANTICIPATED): November 10, 2022

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (ACTUAL): September 10, 2018

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: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: M-2016-312

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