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

  • Interventional
  • Recruiting
  • NCT04450069
Eligibility Details Visit Clinicaltrials.gov

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

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.

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.

Gender
All

Age Group
18 Years and up

Accepting 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

At a Glance

National Government IDNCT04450069

IRB#IRB20-0421

Lead SponsorCalibr, a division of Scripps Research

Lead PhysicianPeter Riedell

Collaborator(s)N/A

EligibilityAll
18 Years and up
Recruiting