Chronic Lymphocytic Leukemia
Conditions
Brief summary
Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab Tesirine to Aclabrutinib in the treatment of chronic lymphocytic leukemia.
Detailed description
The study is a phase I study which will employ the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose (MTD). Approximately 24 Dose-Limiting Toxicity (DLT) evaluable participants will be treated to find MTD with a target DLT rate of 25%, and 4 pre-specified doses. The total number of participants enrolled will depend on the frequency of DLTs and when the MTD is determined. The maximum number of patients at a given dose level is 12. The dose of acalabrutinib will be fixed and loncastuximab tesirine will be titrated as in dose level table 1 below. Table 1. Dose levels Dose Level Schedule 1. 45 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID 2. 60 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID 3. 75 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID 4. 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent cycles) + Acalabrutinib 100 mg BID The DLT evaluation period is two cycles (42 days). Loncastuximab Tesirine will be given as an IV infusion, each cycle is a 21 day cycle, with Loncastuximab Tesirine given day 1 of each cycle.
Interventions
DRUGLoncastuximab Tesirine and Acalabrutinib
Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib
Sponsors
ADC Therapeutics S.A.
University of Alabama at Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential dose escalation based on Dose escalation guidelines.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Inclusion Criteria For all patients 1. Diagnosis of CLL according to the IwCLL criteria or SLL according to the World Health Organization (WHO) criteria. This includes previous documentation of: * Biopsy-proven small lymphocytic lymphoma OR * Diagnosis of CLL according to the IWCLL criteria as evidenced by Peripheral blood lymphocyte count of greater than 5 x109/L . * Immunophenotype consistent with CLL defined as the predominant population of lymphocytes share both B cell antigens (CD19, CD20 (typically dim expression), or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc). 2. On therapy with acalabrutinib for a minimum of 3 months without evidence of progression as per IWCLL 2018 criteria. 3. Relapsed or Refractory CLL who have received at least one prior therapy before initiation of acalabrutinib 4. Presence of measurable residual disease in the peripheral blood or bone marrow aspirate by NGS based clonoseq test. 5. Adequate organ function as defined below unless attributed to disease involvement: * Liver function (bilirubin ≤ 1.5 × ULN, AST and/or ALT \<3 x ULN). Patients with Gilbert Disease are permitted irrespective of bilirubin values. * Kidney function (crcl \> 30ml/min using Cockroft-Gault, based on actual weight). * ANC ≥ 1,000/µL, Hgb \> 8, Platelet Count ≥ 50,000/ µL. Use of G-CSF is not permitted for up to 7 days prior to enrollment.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Objective | 12 months | Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Objective 2 | 12 months | Undetectable measurable residual disease rate (uMRD) at 12 months of combination therapy by NGS based clonoseq test. |
| Secondary Objective 3 | 12 months | Best Overall response rate (ORR = CR+CRi+PR) of loncastuximab tesirine in combination with acalabrutinib |
| Secondary Objective 4 | 12 months | Complete response rate (CRR= CR + CRi) of loncastuximab tesirine in combination with acalabrutinib in achieving a complete response. |
| Secondary Objective 1 | 6 months | undetectable measurable residual disease rate (uMRD) at 6 months of combination therapy in peripheral blood by NGS based clonoseq test |
| Secondary Objective 6 | 12 months | Incidence of adverse events (AE) of loncastuximab tesirine in combination with acalabrutinib. |
| Secondary Objective 7 | 12 months | Duration of response (DOR) of loncastuximab tesirine in combination with acalabrutinib |
| Secondary Objective 5 | 12 months | Progression free survival (PFS) at 12 months after completion of all treatment. |
Countries
United States
Outcome results
None listed