Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia

Trial Title: Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia

NCT ID: NCT05971251

Condition: Chronic Lymphocytic Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Acalabrutinib
Loncastuximab tesirine

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Intervention model description: Sequential dose escalation based on Dose escalation guidelines.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Loncastuximab Tesirine and Acalabrutinib
Description: Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib
Arm group label: Dose Level 1:
Arm group label: Dose Level 2
Arm group label: Dose Level 3
Arm group label: Dose level 4:

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.

Criteria for eligibility:
Criteria:
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: - Exclusion Criteria For all patients 1. Current evidence of central nervous system involvement. 2. Unable to generate clonoseq ID specimen for measurable residual disease tracking. 3. Completion of an autologous hematopoietic stem cell transplantation within 3 months prior to first dose of study drug. 4. Prior allogeneic stem cell transplant within 6 months. The patient should not have any active Graft vs. Host disease (GVH) or should be on immune suppressive agents. 5. Completion of treatment with any radiotherapy, chemotherapy, antibody, immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of the drug, whichever is shorter) prior to the first dose of study drug. Patients may be enrolled after a minimum of 2 weeks of radiation if radiation was for palliative intent. 6. Progression of disease on BTK inhibitor. 7. Unable to tolerate full dose of acalabrutinib at 100 mg twice a day. 8. Inability to swallow and retain oral medications. 9. Pregnant women are excluded from this study. 10. Any active, concurrent, significant illness or disease (other underlying lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participation in the study such as: - active infection requiring systemic therapy ≤10 days before the first dose of study drug - unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug - Significant (as defined by study doctor) pulmonary disease or disorder - any severe or uncontrolled other disease or condition which might increase the risk associated with study participation 11. Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication. 12. Receiving systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). The use of inhaled corticosteroids is permitted. 13. Corticosteroids ≥ 10 mg of prednisone within the last 7 days. 14. Has had a solid organ transplant within the last 3 years. Note: Patients who have had a Solid organ transplant >3 years ago are eligible if there are no signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive medications as per above. 15. Known history of hypersensitivity to loncastuximab tesirine 16. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath) 17. Breastfeeding or pregnant 18. Any other malignancy known to be active, with the exception of - Cervical carcinoma of Stage 1A (1A1,1A2) and 1B (1B1,1B2,1B3) - Non-invasive basal cell or squamous cell skin carcinoma - Non-invasive, superficial bladder cancer - Prostate cancer with a current PSA level < 0.1 ng/mL - Any curable or localized cancer with a CR of > 2 years' duration.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Alabama at Birmingham

Address:
City: Birmingham
Zip: 35294
Country: United States

Status: Recruiting

Contact:
Last name: Mayur Narkhede

Phone: 205-934-4228
Email: msnarkhede@uabmc.edu

Contact backup:
Last name: Pam Dixon

Phone: (205) 975-5387
Email: pamdixon@uab.edu

Investigator:
Last name: Mayur S Narkhede, M.D.
Email: Principal Investigator

Start date: December 18, 2023

Completion date: December 31, 2028

Lead sponsor:
Agency: Mayur Narkhede
Agency class: Other

Collaborator:
Agency: ADC Therapeutics S.A.
Agency class: Industry

Source: University of Alabama at Birmingham

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05971251