Description:
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.
Title
- Brief Title: CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies
- Official Title: A Phase 1, Open-label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the Combination of CLBR001 and SWI019 in Patients With Relapsed/Refractory B-cell Malignancies
Clinical Trial IDs
- ORG STUDY ID:
CBR-sCAR19-3001
- NCT ID:
NCT04450069
Conditions
- Relapsed/Refractory B-cell Lymphomas
- Diffuse Large B Cell Lymphoma (DLBCL)
- Follicular Lymphoma (FL)
- Chronic Lymphocytic Leukemia (CLL)
- Marginal Zone Lymphoma (MZL)
- Mantle Cell Lymphoma
- Small Lymphocytic Lymphoma (SLL)
- Primary Mediastinal Large B Cell Lymphoma
- Transformed Follicular Lymphoma
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation | Experimental | CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD) | |
Eligibility Criteria
Inclusion Criteria:
- Patients with relapsed / refractory previously treated B cell malignancies (according
to the World Health Organization classification; 2017)
- Chemotherapy-refractory disease
- Patients must have received adequate prior therapy including at least two lines of
prior therapies including anthracycline-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 disease histologies including pediatric lymphomas/leukemias,
Burkitt lymphoma, lymphoplasmacytic lymphomas, 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 CD19 or CD20 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events |
Time Frame: | 35 days |
Safety Issue: | |
Description: | To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events |
Secondary Outcome Measures
Measure: | Maximum drug concentration (Cmax) of SWI019 |
Time Frame: | up to Day 35 |
Safety Issue: | |
Description: | To determine the maximum concentration of SWI019 in a patient's peripheral blood |
Measure: | Area under the curve (AUC) of SWI019 |
Time Frame: | up to Day 35 |
Safety Issue: | |
Description: | To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time |
Measure: | Time to reach Cmax (Tmax) of SWI019 |
Time Frame: | up to Day 35 |
Safety Issue: | |
Description: | To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood |
Measure: | Clearance (CL) of SWI019 |
Time Frame: | up to Day 35 |
Safety Issue: | |
Description: | To determine the clearance factor of SWI019 in a patient's peripheral blood |
Measure: | Apparent elimination half-life (t1/2) of SWI019 |
Time Frame: | up to Day 35 |
Safety Issue: | |
Description: | To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood |
Measure: | Quantification of CLBR001 cells in peripheral blood |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To quantify CLBR001 in a patient's peripheral blood at different time points |
Measure: | Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry |
Measure: | Immunogenic response to CLBR001 |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood |
Measure: | Immunogenic response to SWI019 |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood |
Measure: | Serum cytokine concentrations |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | 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 |
Measure: | Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria |
Measure: | Duration of response (DOR) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration |
Measure: | Progression free survival (PFS) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the duration of patient's progression-free survival |
Measure: | Overall survival (OS) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | To evaluate the overall duration of patient's survival |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Calibr, a division of Scripps Research |
Trial Keywords
- CAR-T Cell Therapy
- Switchable CAR-T Cell
- Autologous Cell Therapy
- CD19 Positive Disease
- CD19 CAR-T Cell
- Blood Cancer
- Hematological malignancy
- Neoplasms
Last Updated
May 18, 2021