MB-CART20.1 Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03664635
• Other study ID #: M-2016-312
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 25, 2018
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Miltenyi Biomedicine GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Lymphoma Recurrent
• B-cell Lymphoma Refractory
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma
• Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Intervention

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

Locations

Country	Name	City	State
Germany	University Hospital of Cologne - Clinic for Internal Medicine I	Cologne
Germany	Universitätsklikum Leipzig, AöR	Leipzig

Sponsors (1)

Lead Sponsor	Collaborator
Miltenyi Biomedicine GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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