Chronic Lymphocytic LeukemiaPhase 1NCT05971251
Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia
A Phase 1 study testing Loncastuximab Tesirine and Acalabrutinib in people with Chronic Lymphocytic Leukemia, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Loncastuximab Tesirine and Acalabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2023to 31 Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Addition of loNcasTuxImab teSirine to AcalabruTinib in Chronic Lymphocytic Leukemia(Anti-Static Study)
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.
Read the 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
- 45 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 60 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 75 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 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.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Loncastuximab Tesirine and Acalabrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Loncastuximab Tesirine and AcalabrutinibDrug
Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1: | Experimental | 45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles Receives: Drug: Loncastuximab Tesirine and Acalabrutinib |
| Dose Level 2 | Experimental | 60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles Receives: Drug: Loncastuximab Tesirine and Acalabrutinib |
| Dose Level 3 | Experimental | 75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles Receives: Drug: Loncastuximab Tesirine and Acalabrutinib |
| Dose level 4: | Experimental | 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent 10 cycles) + Acalabrutinib 100 mg BID for a total of 12 cycles. Receives: Drug: Loncastuximab Tesirine and Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Objective
Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib
Measured: 12 months
Secondary outcomes (7)
Secondary Objective 1
undetectable measurable residual disease rate (uMRD) at 6 months of combination therapy in peripheral blood by NGS based clonoseq test
Measured: 6 months
Secondary Objective 2
Undetectable measurable residual disease rate (uMRD) at 12 months of combination therapy by NGS based clonoseq test.
Measured: 12 months
Secondary Objective 3
Best Overall response rate (ORR = CR+CRi+PR) of loncastuximab tesirine in combination with acalabrutinib
Measured: 12 months
Secondary Objective 4
Complete response rate (CRR= CR + CRi) of loncastuximab tesirine in combination with acalabrutinib in achieving a complete response.
Measured: 12 months
Secondary Objective 5
Progression free survival (PFS) at 12 months after completion of all treatment.
Measured: 12 months
Secondary Objective 6
Incidence of adverse events (AE) of loncastuximab tesirine in combination with acalabrutinib.
Measured: 12 months
Secondary Objective 7
Duration of response (DOR) of loncastuximab tesirine in combination with acalabrutinib
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start18 Dec 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Sequential dose escalation based on Dose escalation guidelines.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- ADC Therapeutics S.A.
- Responsible party
- Principal investigator, Aditi Saha, MD, University of Alabama at Birmingham
- Investigators
- Aditi Saha, M.D., Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05971251
- Sponsor's protocol ID
- IRB-300009213
- Other IDs
- 000549077
- Status last verified
- Oct 2026
- First submitted
- 14 Jul 2023
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No