CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies
Primary Purpose
Relapsed/Refractory B-cell Lymphomas, Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL)
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CLBR001 and SWI019
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory B-cell Lymphomas focused on measuring CAR-T Cell Therapy, Switchable CAR-T Cell, Autologous Cell Therapy, CD19 Positive Disease, CD19 CAR-T Cell, Blood Cancer, Hematological malignancy, Neoplasms
Eligibility Criteria
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
Sites / Locations
- City of Hope National Medical Center
- University of California at San Diego
- University of Chicago
- Masonic Cancer Center, University of Minnesota
- Weill Cornell Medical College - New York Presbyterian Hospital
- Wake Forest Baptist Health
- Sarah Cannon Research Institute - Tennessee Oncology
- Sarah Cannon Research Institute - Texas Transplant Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation
Arm Description
CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)
Outcomes
Primary Outcome Measures
Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
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)
Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)
Secondary Outcome Measures
Maximum drug concentration (Cmax) of SWI019
To determine the maximum concentration of SWI019 in a patient's peripheral blood
Area under the curve (AUC) of SWI019
To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
Time to reach Cmax (Tmax) of SWI019
To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
Clearance (CL) of SWI019
To determine the clearance factor of SWI019 in a patient's peripheral blood
Apparent elimination half-life (t1/2) of SWI019
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
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
To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
Immunogenic response to CLBR001
To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
Immunogenic response to SWI019
To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
Serum cytokine concentrations
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
To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
Duration of response (DOR)
To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
Progression free survival (PFS)
To evaluate the duration of patient's progression-free survival
Overall survival (OS)
To evaluate the overall duration of patient's survival
Full Information
NCT ID
NCT04450069
First Posted
June 23, 2020
Last Updated
June 27, 2023
Sponsor
Calibr, a division of Scripps Research
1. Study Identification
Unique Protocol Identification Number
NCT04450069
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 14, 2020 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Calibr, a division of Scripps Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma, Burkitt Lymphoma
Keywords
CAR-T Cell Therapy, Switchable CAR-T Cell, Autologous Cell Therapy, CD19 Positive Disease, CD19 CAR-T Cell, Blood Cancer, Hematological malignancy, Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)
Intervention Type
Combination Product
Intervention Name(s)
CLBR001 and SWI019
Intervention Description
Investigational immunotherapy for B cell malignancies
Primary Outcome Measure Information:
Title
Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
Description
To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
Time Frame
35 days
Title
Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Description
Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)
Time Frame
up to 1 year
Secondary Outcome Measure Information:
Title
Maximum drug concentration (Cmax) of SWI019
Description
To determine the maximum concentration of SWI019 in a patient's peripheral blood
Time Frame
up to Day 35
Title
Area under the curve (AUC) of SWI019
Description
To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
Time Frame
up to Day 35
Title
Time to reach Cmax (Tmax) of SWI019
Description
To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
Time Frame
up to Day 35
Title
Clearance (CL) of SWI019
Description
To determine the clearance factor of SWI019 in a patient's peripheral blood
Time Frame
up to Day 35
Title
Apparent elimination half-life (t1/2) of SWI019
Description
To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
Time Frame
up to Day 35
Title
Quantification of CLBR001 cells in peripheral blood
Description
To quantify CLBR001 in a patient's peripheral blood at different time points
Time Frame
up to 1 year
Title
Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies
Description
To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
Time Frame
up to 1 year
Title
Immunogenic response to CLBR001
Description
To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
Time Frame
up to 1 year
Title
Immunogenic response to SWI019
Description
To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
Time Frame
up to 1 year
Title
Serum cytokine concentrations
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
Time Frame
up to 1 year
Title
Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria
Description
To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
Time Frame
up to 1 year
Title
Duration of response (DOR)
Description
To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
Time Frame
up to 1 year
Title
Progression free survival (PFS)
Description
To evaluate the duration of patient's progression-free survival
Time Frame
up to 1 year
Title
Overall survival (OS)
Description
To evaluate the overall duration of patient's survival
Time Frame
up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California at San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Weill Cornell Medical College - New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Sarah Cannon Research Institute - Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Sarah Cannon Research Institute - Texas Transplant Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26759369
Citation
Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, Schulman A, Du J, Wang F, Singer O, Ma J, Nunez V, Shen J, Woods AK, Wright TM, Schultz PG, Kim CH, Young TS. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68. doi: 10.1073/pnas.1524155113. Epub 2016 Jan 12.
Results Reference
background
PubMed Identifier
30373813
Citation
Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, Nunez V, Ackerman CJ, Khialeeva E, Weglarz M, Lee SC, Woods AK, Young TS. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10898-E10906. doi: 10.1073/pnas.1810060115. Epub 2018 Oct 29.
Results Reference
background
PubMed Identifier
34515338
Citation
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Results Reference
derived
Learn more about this trial
CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies
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