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.

Conditions: Chronic Lymphocytic Leukaemia (CLL); Small Lymphocytic Lymphoma (SLL)

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.

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.

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 * no contraindications for leukapheresis * left ventricular ejection fraction \>50% * gives informed consent 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

Keywords: anti-cd19 car t-cells lenalidomide ibrutinib