Chronic Lymphocytic Leukaemia (CLL), Small Lymphocytic Lymphoma (SLL)
Conditions
Keywords
anti-CD19 CAR T-cells, Lenalidomide, Ibrutinib
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
Patients receive ibrutinib 420 mg daily for 3 months before CAR T-cell infusion. Obinutuzumab 1000 mg is administered 14 days before leukapheresis to reduce circulating CLL cells. Lymphodepletion consists of fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² on days -5 to -3. In a 3+3 dose-escalation design, patients receive a single infusion of 25 × 10⁶ (DL1), 50 × 10⁶ (DL2), or 100 × 10⁶ (DL3) autologous CD19 CAR T cells. Lenalidomide 10 mg is administered orally on days 0 through 6. At day 28, patients with measurable residual disease (MRD)-positive disease are eligible for lenalidomide 10 mg 1-14 days per os plus obinutuzumab 1000 mg IV 1,8,15 days on cycle 1 and on day 1 on 2-6 cycles consolidation, whereas patients with MRD-negative disease receive lenalidomide 10 mg per os 1-14 days maintenance for 3 cycles. 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. * Progression-free survival rates. * Overall survival rates. * MRD negativity rates measured by flow cytometry.
Interventions
DRUGLenalidomide
Lenalidomide 10mg per os 0- 6 days
BIOLOGICALObinutuzumab Injection [Gazyva]
Combined with Lenalidomide 10 mg per os 1- 14 days for 6 cycles
Sponsors
Vitebsk Regional Clinical Cancer Centre
Republican Scientific and Practical Center for children's Oncology, Hematology and Immunology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events incidence | 24 months | — |
| Safety | 24 months | * 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. |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy | - Overall response rate, including complete response (CR) and partial response (PR) rates. - Progression-free survival rates. - Overall survival rates. - MRD negativity rates measured by flow cytometry. |
Countries
Belarus
Contacts
CONTACTMikalai Katsin
Outcome results
None listed