Burkitt Lymphoma, Chronic Lymphocytic Leukemia (CLL), Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma (MZL), Primary Mediastinal Large B Cell Lymphoma, Relapsed/Refractory B-cell Lymphomas, Small Lymphocytic Lymphoma (SLL), Transformed Follicular Lymphoma, Waldenstrom Macroglobulinemia
Conditions
Keywords
CAR-T Cell Therapy, Switchable CAR-T Cell, Autologous Cell Therapy, CD19 Positive Disease, CD19 CAR-T Cell, Blood Cancer, Hematological malignancy, Neoplasms
Brief summary
CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.
Detailed description
CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic). In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.
Interventions
COMBINATION_PRODUCTCLBR001 and SWI019
Investigational immunotherapy for B cell malignancies
Sponsors
Calibr, a division of Scripps Research
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with relapsed / refractory previously treated B cell malignancies (according to the World Health Organization classification; 2017) * Patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-containing chemotherapy, anti-CD20 (cluster of differentiation antigen 20) therapies and/or Brutton's tyrosine kinase (BTK) inhibitors * Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have confirmed CD19+ disease * Patients must be ineligible for allogeneic stem cell transplant (SCT) * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 * Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered * Willing to undergo pre- and post-treatment core needle biopsy * Adequate hematological, renal, pulmonary, cardiac, and liver function * Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1 * Women of childbearing potential, a negative pregnancy test and must agree to practice effective birth control * Men sexually active with female partners of child bearing potential must agree to practice effective contraception * Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures
Exclusion criteria
* Patients diagnosed with certain disease histologies including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance (MGUS), T-cell histiocyte large B cell lymphoma * Pregnant or lactating women * Active bacterial, viral, and fungal infections * History of allogeneic stem cell transplantation * Treatment with any prior lentiviral or retroviral based CAR-T * Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or need for live vaccine on study * Patients with known active central nervous system (CNS) disease. Patients with prior CNS disease that has been effectively treated may be eligible * History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial infarction, unstable angina or other significant cardiac disease within 6 months of screening * Involvement of cardiac tissue by lymphoma * Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) * HIV-1 and HIV-2 antibody positive patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events | 35 days | To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events |
| Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) | up to 1 year | Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach Cmax (Tmax) of SWI019 | up to Day 35 | To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood |
| Clearance (CL) of SWI019 | up to Day 35 | To determine the clearance factor of SWI019 in a patient's peripheral blood |
| Apparent elimination half-life (t1/2) of SWI019 | up to Day 35 | To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood |
| Quantification of CLBR001 cells in peripheral blood | up to 1 year | To quantify CLBR001 in a patient's peripheral blood at different time points |
| Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies | up to 1 year | To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry |
| Immunogenic response to CLBR001 | up to 1 year | To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood |
| Maximum drug concentration (Cmax) of SWI019 | up to Day 35 | To determine the maximum concentration of SWI019 in a patient's peripheral blood |
| Serum cytokine concentrations | up to 1 year | To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points |
| Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria | up to 1 year | To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria |
| Duration of response (DOR) | up to 1 year | To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration |
| Progression free survival (PFS) | up to 1 year | To evaluate the duration of patient's progression-free survival |
| Overall survival (OS) | up to 1 year | To evaluate the overall duration of patient's survival |
| Immunogenic response to SWI019 | up to 1 year | To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood |
| Area under the curve (AUC) of SWI019 | up to Day 35 | To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time |
Countries
United States
Outcome results
None listed