Status:
ACTIVE_NOT_RECRUITING
Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia
Lead Sponsor:
University of Alabama at Birmingham
Collaborating Sponsors:
ADC Therapeutics S.A.
Conditions:
Chronic Lymphocytic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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 participan...
Eligibility Criteria
Inclusion
- \- Inclusion Criteria For all patients
- 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).
- On therapy with acalabrutinib for a minimum of 3 months without evidence of progression as per IWCLL 2018 criteria.
- Relapsed or Refractory CLL who have received at least one prior therapy before initiation of acalabrutinib
- Presence of measurable residual disease in the peripheral blood or bone marrow aspirate by NGS based clonoseq test.
- 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
- Exclusion Criteria For all patients
- Current evidence of central nervous system involvement.
- Unable to generate clonoseq ID specimen for measurable residual disease tracking.
- Completion of an autologous hematopoietic stem cell transplantation within 3 months prior to first dose of study drug.
- 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.
- 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.
- Progression of disease on BTK inhibitor.
- Unable to tolerate full dose of acalabrutinib at 100 mg twice a day.
- Inability to swallow and retain oral medications.
- Pregnant women are excluded from this study.
- 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
- Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication.
- 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.
- Corticosteroids ≥ 10 mg of prednisone within the last 7 days.
- 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.
- Known history of hypersensitivity to loncastuximab tesirine
- 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)
- Breastfeeding or pregnant
- 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.
Key Trial Info
Start Date :
December 18 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2028
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT05971251
Start Date
December 18 2023
End Date
December 31 2028
Last Update
October 1 2025
Active Locations (1)
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1
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294