Description:
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.
Title
- Brief Title: MB-CART20.1 Lymphoma
- 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 IDs
- ORG STUDY ID:
M-2016-312
- NCT ID:
NCT03664635
Conditions
- Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
- Non-Hodgkin's Lymphoma
- B-cell Lymphoma Refractory
- B-cell Lymphoma Recurrent
Interventions
Drug | Synonyms | Arms |
---|
MB-CART20.1 | CD20-targeting CAR T Cells, Anti-CD20 CAR T cells | Phase I - Dose Level 1 |
Purpose
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)
Trial Arms
Name | Type | Description | Interventions |
---|
Phase I - Safety Dose Level | Experimental | 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 | |
Phase I - Dose Level 1 | Experimental | 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 | |
Phase I - Dose Level 2 | Experimental | 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 | |
Phase II | Experimental | 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 | |
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase I - Determination of the maximum tolerated dose (MTD) |
Time Frame: | until day 28 after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Phase I - Related safety and toxicity of MB-CART20.1 |
Time Frame: | months 3, 6, 9 and 12 after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Per adverse events (AE) reporting classified according to CTCAE version 5.0. |
Measure: | 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 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase I - Best overall response rate over 1 year |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase I - Occurrence of B-cell aplasia |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry. |
Measure: | Phase I - Phenotype and Persistence of MB-CART20.1 |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed. |
Measure: | Phase II - Best overall response rate over 1 year |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase II - Overall response rate over 4 weeks and 3 months |
Time Frame: | 4 weeks and 3 months after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase II - Overall response rate over 1 year |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase II - Number of patients with CR, PR, SD and PD |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase II -Percentage of patients with CR, PR, SD and PD |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Measure: | Phase II - Safety and toxicity assessment of MB-CART20.1 |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Per adverse events (AE) reporting classified according to CTCAE version 5.0. |
Measure: | Phase II - Occurrence of B-cell aplasia |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry. |
Measure: | Phase II - Phenotype and Persistence of MB-CART20.1 |
Time Frame: | 1 year after infusion of MB-CART20.1 |
Safety Issue: | |
Description: | Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Miltenyi Biomedicine GmbH |
Last Updated
March 8, 2019