DALY 2.0 USA/ MB-CART2019.1 for DLBCL
Study Details
Study Description
Brief Summary
This is an open label, single arm, phase II study to determine the efficacy, safety and PK (persistence) of MBCART2019.1 cells in adults with relapsed or refractory DLBCL after receiving at least two lines of therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
A prospective, single arm, open label, multi-center, phase II study of autologous T cells engineered against both CD19 and CD20 antigens for subjects with relapsed or refractory DLBCL after receiving at least two lines of therapy. The investigational agent is the MB-CART2019.1 cells. After successful screening, subjects will undergo leukapheresis to collect product for manufacturing. In preparation for the fresh product infusion, subjects will undergo a lymphodepleting regimen with cyclophosphamide and fludarabine. Cell infusion will be administered intravenously at a dose of 2.5 x 106 CAR+ cells/kg body weight. The study will start with enrollment of 3 subjects in the lead-in safety phase, and after safety is evaluated, the study will continue with enrollment of the remaining subjects. Subjects will be followed for up to 2 years, for efficacy and safety outcomes as well as health-related quality of life (HRQol). Additional long-term follow-up will be conducted for participants under a separate long-term follow-up protocol.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single, open label
|
Biological: MB-CART2019.1
Chimeric antigen receptor (CAR) T cell therapy
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [1 month]
ORR
Secondary Outcome Measures
- Complete Response Rate [6 months]
CRR
- Duration of Response [Up to 2 years]
DOR
- Overall Response Rate [6 months]
ORR
- Best Overall Response [2 years]
BOR
- Progression Free Survival [Up to 2 years]
PFS
- Overall Survival [Up to 2 years]
OS
- Type, frequency, and severity of adverse events [Up to 2 years]
Safety
- Incidence of anti-MD-CART2019.1 antibodies [Up to 2 years]
Bioanalytical
- Phenotype of MB-CART2019.1 [Up to 2 years]
Bioanalytical
- Persistence of MB-CART2019.1 [Up to 2 years]
Bioanalytical
- Quality of Life (QoL) assessments [EQ-5D-5L] [Up to 2 years]
Health Outcomes - Standardized 5 question measure of health status developed by the EuroQol Group
- Patient-Reported Outcome (PRO) assessment [FACT-Lym] [Up to 2 years]
Health Outcomes - To address health-related quality-of-life (HRQL) issues for Non-Hodgkin's lymphoma (NHL) patients
- Pharmacodynamics [Levels of cytokines in blood] [Up to 2 years]
Bioanalytical
- Correlation of tumor CD19 and CD20 antigen expression with disease progression and relapse [Up to 2 years]
Bioanalytical
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification
-
Relapsed or Refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or being ineligible for or not consenting to ASCT
-
Age > 18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL
-
Measurable disease according to Lugano 2014 criteria for assessing FDG PET/CT in lymphoma (Cheson et al, 2014)
-
Subject must have a tumor biopsy sample, per protocol specified slide availability from the most recent relapse available prior to MBCART2019.1 Infusion. If medically not feasible to obtain biopsy from the most recent relapse and for cases when amount of tissue is limited, sponsor should be consulted, to confirm adequacy of sample for study required analyses.
-
No clinical suspicion of CNS lymphoma
-
If the subject has history of CNS disease, then he/she must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI) and have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs)
-
If has history of cerebral vascular accident (CVA), the CVA must be greater than 12 months prior to leukapheresis and any neurological deficits must be stable
-
A creatinine clearance (as estimated either by a direct urine collection or Cockcroft-Gault Equation) > 60mL/min
-
Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
-
Resting O2 saturation >90% on room air
-
Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 times the Upper Limit of Normal (ULN) for age
-
Total bilirubin <1.5 mg/dl, except in individuals with Gilbert's syndrome
-
Absolute neutrophil count > 1000/μL
-
Absolute lymphocyte count > 100/μL
-
Platelet count > 50,000/μL
-
Estimated life expectancy of more than 3 months other than primary disease
-
Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study.
Exclusion Criteria:
-
Primary CNS lymphoma
-
Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL)
-
Unable to give informed consent
-
Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive.
-
Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing
-
Known history of active seizures or presence of seizure activities or on active, anti-seizure medications within the prior 12 months
-
Known history of CVA within prior 12 months.
-
Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease
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Presence of CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity
-
Active systemic fungal, viral, or bacterial infection
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Pregnant or breast-feeding woman
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Previous or concurrent malignancy with the following exceptions:
-
Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)
-
In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
-
Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years
-
A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
-
History of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus)requiring systemic immunosuppressive or system disease modifying agents within the last 2 years
-
Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day
-
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
-
Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis
-
Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline
-
History of severe immediate hypersensitivity reaction to any of the agents used in this study
-
Refusal to participate in additional lentiviral gene therapy LTFU protocol
-
Prior CAR-T therapy for any indication or systemic gene modifying therapy for DLBCL
-
Prior allogeneic stem cell transplant for any indication
-
Prior BITE antibodies for cancer therapy
-
Prior T cell receptor-engineered T cell therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner MD Anderson Cancer Center | Gilbert | Arizona | United States | 85234 |
| 2 | Mayo Clinic | Phoenix | Arizona | United States | 85054 |
| 3 | Stanford University | Stanford | California | United States | 94305 |
| 4 | Yale University | New Haven | Connecticut | United States | 06520 |
| 5 | University of Kansas Cancer Center | Westwood | Kansas | United States | 66205 |
| 6 | University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center | Baltimore | Maryland | United States | 21201 |
| 7 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 8 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 9 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 10 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 11 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 12 | Duke University Medical Center - Division of Hematologic Malignancies | Durham | North Carolina | United States | 27705 |
| 13 | Oregon Health and Science University Knight Cancer Institute | Portland | Oregon | United States | 97239 |
| 14 | University of Pittsburgh - Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15260 |
| 15 | Froedtert Hospital and the Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Miltenyi Biomedicine GmbH
Investigators
- Study Director: Remi Kaleta, Miltenyi Biomedicine GmbH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M-2018-344