CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies

• ClinicalTrials.gov Identifier: NCT04450069
• Recruitment Status: Active, not recruiting
• First Posted: June 29, 2020
• Last Update Posted: January 24, 2024
• Sponsor: Calibr, a division of Scripps Research
• Information provided by (Responsible Party): Calibr, a division of Scripps Research

Tracking Information

• First Submitted Date: June 23, 2020
• First Posted Date: June 29, 2020
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: August 14, 2020
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2020)

• Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events [ Time Frame: 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) [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 26, 2020)

• Maximum drug concentration (Cmax) of SWI019 [ Time Frame: up to Day 35 ]
  To determine the maximum concentration of SWI019 in a patient's peripheral blood
• Area under the curve (AUC) of SWI019 [ Time Frame: up to Day 35 ]
  To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
• Time to reach Cmax (Tmax) of SWI019 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to 1 year ]
  To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
• Immunogenic response to SWI019 [ Time Frame: up to 1 year ]
  To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
• Serum cytokine concentrations [ Time Frame: 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 [ Time Frame: up to 1 year ]
  To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
• Duration of response (DOR) [ Time Frame: up to 1 year ]
  To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
• Progression free survival (PFS) [ Time Frame: up to 1 year ]
  To evaluate the duration of patient's progression-free survival
• Overall survival (OS) [ Time Frame: up to 1 year ]
  To evaluate the overall duration of patient's survival

Original Secondary Outcome Measures (submitted: June 25, 2020)

• Maximum drug concentration (Cmax) of SWI019 [ Time Frame: up to Day 35 ]
  To determine the maximum concentration of SWI019 in a patient's peripheral blood
• Area under the curve (AUC) of SWI019 [ Time Frame: up to Day 35 ]
  To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
• Time to reach Cmax (Tmax) of SWI019 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to 1 year ]
  To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
• Immunogenic response to SWI019 [ Time Frame: up to 1 year ]
  To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
• Serum cytokine concentrations [ Time Frame: up to 1 year ]
  To measure the cytokine levels 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 [ Time Frame: up to 1 year ]
  To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
• Duration of response (DOR) [ Time Frame: up to 1 year ]
  To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
• Progression free survival (PFS) [ Time Frame: up to 1 year ]
  To evaluate the duration of patient's progression-free survival
• Overall survival (OS) [ Time Frame: up to 1 year ]
  To evaluate the overall duration of patient's survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

Combination Product: CLBR001 and SWI019

Investigational immunotherapy for B cell malignancies

Study Arms

Experimental: Dose Escalation

CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)

Intervention: Combination Product: CLBR001 and SWI019

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 23, 2024): 18
• Original Estimated Enrollment (submitted: June 25, 2020): 36
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04450069
• Other Study ID Numbers: CBR-sCAR19-3001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Calibr, a division of Scripps Research
• Original Responsible Party: Same as current
• Current Study Sponsor: Calibr, a division of Scripps Research
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Calibr, a division of Scripps Research
• Verification Date: January 2024