Phase I/II Open-label Study Evaluating The Safety And Efficacy of Concomitant Administration of Anti-CD19 CAR T-cell Therapy and Lenalidomide in Refractory/Relapsed Chronic Lymphocytic Leukemia Patients.
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- Chronic Lymphocytic Leukaemia (CLL)
- Sponsor
- Vitebsk Regional Clinical Cancer Centre
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Adverse events incidence
- Status
- Enrolling by Invitation
- Last Updated
- last year
Overview
Brief Summary
This is a Phase I/II interventional, open-label treatment study designed to evaluate the safety and efficacy of concomitant therapy with anti-CD19 CAR T-cells and Lenalidomide in adult patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have been pretreated with Ibrutinib for 3 months prior to leukapheresis.
Detailed Description
This is a single-center, open-label study. After meeting the eligibility criteria and enrolling in the trial, patients will take Ibrutinib for 3 months up to Day -1. Leukapheresis for the collection of autologous lymphocytes will take place 2-3 weeks before Day 0. Once the cells have been manufactured, patients will proceed to lymphodepleting chemotherapy with cyclophosphamide and fludarabine from Days -5 to -3, followed by the infusion of anti-CD19-4-1BB-CD3z CAR T-cells at two fixed dose levels: DL1 (50 x 10\^6 cells) and DL2 (150 x 10\^6 cells), concomitantly with Lenalidomide intake. Lenalidomide maintenance at the dose of 25 mg will be administered from Day +30 for 3 months. The main purposes of the Phase I part are: * To preliminarily explore the safety (incidence of CRS, ICANS, HLH, infections, late ICAHT, and cytopenias) and tolerability. * To explore the pharmacokinetics of CAR-T cells. The main purposes of the Phase II part are: * Overall response rate, including complete response (CR) and partial response (PR) rates. * Duration of response (DOR). * Progression-free survival rates. * Overall survival rates. * MRD negativity rates measured by flow cytometry.
Investigators
Mikalai Katsin
Chief of Hematology/Oncology department
Vitebsk Regional Clinical Cancer Centre
Eligibility Criteria
Inclusion Criteria
- •Documented CD19+ CLL or SLL
- •Patients must have failed at least 1 prior regimen
- •Patients must be currently receiving ibrutinib for at least 3 months prior to enrollment in the study and:
- •Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity
- •ECOG Performance status 0 or 1
- •18 years of age and older
- •Adequate organ system function including:
- •Creatinine \< 1.6 mg/dl ALT/AST \< 3x upper limit of normal Total Bilirubin \<2.0 mg/dl with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
- •Have no active GVHD and require no immunosuppression
- •Are more than 6 months from transplant
Exclusion Criteria
- •CLL patients with known or suspected transformed disease (i.e. Richter's transformation).
- •Pregnant or lactating women.
- •Uncontrolled active infection.
- •Active hepatitis B or hepatitis C infection.
- •Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
- •Any uncontrolled active medical disorder
- •HIV infection.
- •Patients with active CNS involvement with malignancy.
- •Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- •Subjects with clinically apparent arrhythmia or arrhythmias who are not stable
Arms & Interventions
Low dose antiCD19 CAR T-cells plus low dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 50x10\^6 antiCD19 CAR-T cells with concomitant low dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 patients.
Intervention: Lenalidomide
Low dose antiCD19 CAR T-cell therapy plus high dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 50x10\^6 antiCD19 CAR-T cells with concomitant high dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Intervention: Lenalidomide
High dose antiCD19 CAR T-cell therapy plus low dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 150x10\^6 antiCD19 CAR-T cells with concomitant low dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Intervention: Lenalidomide
High dose antiCD19 CAR T-cell therapy plus high dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 150x10\^6 antiCD19 CAR-T cells with concomitant high dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Adverse events incidence
Time Frame: 24 months