Lymphomas Non-Hodgkin's B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions
Keywords
Gene Therapy
Brief summary
The purpose of this first-in-human study is to evaluate the safety and tolerability of INT2104 when administered to humans in a broad population of participants with refractory/relapsing B-cell malignancies. Preliminary efficacy information may also be obtained. INT2104 is a gene therapy delivering a transgene for a chimeric antigen receptor (CAR) specific for CD20 (CAR20). The lentiviral vector is designed to generate CAR T and CAR Natural Killer (NK) cells inside the body following intravenous (IV) administration. Study details include the following: * The study duration will be 5 years * The treatment duration will be a one-time intravenous (IV) infusion of INT2104
Detailed description
This is a non-randomized, open label, multi-site, Phase 1 First in Human (FIH) study split into two parts. The first part (Part A) is a dose escalation and the second part (Part B) will be to confirm the dose. The aim of the study is to collect data to assess whether the study product, INT2104, is safe and tolerable, to understand how well INT2104 works in the human body and to select the dose to take into a Phase 2 study. All participants will receive one intravenous (IV) infusion of INT2104. Each participant in the study will follow the same study treatment schedule and will proceed through the following study periods: * Screening Period: participant will be assessed for eligibility * Study Day 1: participants who meet all eligibility criteria will receive INT2104 by a one-time infusion * Post-treatment Assessment Period: participants will be followed regularly with clinic visits after they receive INT2104
Interventions
GENETICINT2104
INT2104 is a lentiviral vector delivering a transgene for a chimeric antigen receptor specific for CD20 (CAR20)
Sponsors
Kite, A Gilead Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with relapsed/refractory (R/R) B-NHL (Burkitt's lymphoma are eligible for Part B only) confirmed by histology or flow cytometry Note: Bone Marrow involvement is allowed * B-NHL must have CD20 antigen positive tumour confirmed from a tumour biopsy taken at screening * Measurable disease at the time of enrolment * Progression after at least 2 lines of systemic therapy * Has not received more than one prior marketed CAR-T cell therapy (including tandem or bispecific CAR-T) or other genetically modified T-cell therapy. * Sex and Contraceptive/Barrier Requirements consistent with local regulations for clinical trials Females: must have negative serum pregnancy test at screening and on Day -1 prior to INT2104 infusion Both sexes: must agree to use highly effective methods, including a barrier method after INT2104 infusion * Haematological criteria: * Absolute lymphocyte count (ALC) ≥300/µL * Platelet count ≥50,000/mL * Absolute neutrophil count (ANC) ≥500/µL * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Adequate renal, cardiac, hepatic, and lung function Key Inclusion Part B only * Diagnosed with relapsed/refractory B-ALL, and with exceptions as detailed in
Exclusion criteria
. Participants with Philadelphia chromosome positive (Ph+) B-ALL disease are eligible. * B-ALL participants must have CD20 antigen positive leukaemia * Measurable disease at the time of enrolment * Participants with Burkitt's lymphoma are eligible for Part B only
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | Up to 5 years | Number of Participants With Adverse Events as Assessed by CTCAE v5.0 |
| Number of Participants With Abnormal Clinical Laboratory Values and Physical Examination Results | Baseline, up to Day 29 | Number of Participants With abnormal clinical laboratory values as Assessed by CTCAE v5.0 |
| Number of Participants Experiencing Cytokine Release Syndrome (CRS) | Baseline, up to Day 29 | Number of participants experiencing Cytokine Release Syndrome (CRS) |
| Number of Participants Experiencing Immune Effector Cell Neurotoxicity (ICANS) | 28 Days | Number of participants experiencing Immune Effector Cell Neurotoxicity (ICANS) |
| Number of Participants Experiencing dose-limiting toxicities (DLTs) | 28 Days | Number of participants experiencing dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame |
|---|---|
| Levels of Vector Ribonucleic Acid (RNA) Genomes in Blood Over Time | Baseline, up to Day 29 |
| Levels of Transgene Deoxyribonucleic Acid (DNA) Copies in Blood Over Time | Baseline, up to Day 29 |
| Levels of CD20-targeting Chimeric Antigen Receptor (CAR20) Positive T Cells in Blood Over Time | Baseline, up to Day 29 |
| Levels of Natural Killer (NK) Cells in Blood Over Time | Baseline, up to Day 29 |
| Number of Participants with CAR20-positive Cells in Accessible Tumour Tissue Over Time | Baseline, up to Day 29 |
| Change in the Levels of Lymphocyte Subsets Including B-cell Counts Over Time | Baseline, up to Day 29 |
| Objective Response Rate (ORR) as Determined by Investigator Assessment | Day 90 |
| Complete Response (CR) Rate as Determined by Investigator Assessment | Day 90 |
| Duration of response (DOR) as Determined by Investigator Assessment | Up to 5 years |
| Progression Free Survival (PFS) as Determined by Investigator Assessment | Up to 5 years |
| Overall Survival (OS) as Determined by Investigator Assessment | Up to 5 years |
| Number of Participants with Cytokine Release Syndrome (CRS) | Up to 5 years |
| Number of Participants with Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) | Up to 5 years |
| Duration of Cytokine Release Syndrome (CRS) | Up to 5 years |
| Duration of ICANS | Up to 5 years |
| Number of Participants with Vector-derived Replication Competent Lentivirus (RCL) Through Year 5 | Up to 5 years |
| Assessment of Humoral Immunity: Number of Participants with Anti-CAR and Anti-vector Antibodies Over Time | Up to 5 years |
| Assessment of Cellular Immunity: Number of Participants with Changes in T-cell Enzyme-Linked Immunospot Assay (ELISPOT) and Cytokine Profiles Over Time | Up to 5 years |
| Assessment of Vector Shedding: Number of Participants with Vector Shedding in Saliva, Faeces, and Urine Over Time | Up to 5 years |
Countries
Australia, Spain
Contacts
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Outcome results
None listed