Addition of Loncastuximab Tesirine to Acalbrutinib , Chronic Lymphocytic Leukemia

NCT05971251 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-300009213000549077
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Primary Objective

  Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib

  12 months

Secondary Outcomes (7)

• Secondary Objective 1

  6 months

• Secondary Objective 2

  12 months

• Secondary Objective 3

  12 months

• Secondary Objective 4

  12 months

• Secondary Objective 5

  12 months

Study Arms (4)

Dose Level 1:

EXPERIMENTAL

45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

Drug: Loncastuximab Tesirine and Acalabrutinib

Dose Level 2

EXPERIMENTAL

60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

Drug: Loncastuximab Tesirine and Acalabrutinib

Dose Level 3

EXPERIMENTAL

75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

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.

Drug: Loncastuximab Tesirine and Acalabrutinib

Interventions

Loncastuximab Tesirine and Acalabrutinib DRUG

Will be given on Day 1 of each cycle with each cycle being 21 days, and is being added to BID Acalabrutinib

Dose Level 1:; Dose Level 2; Dose Level 3; Dose level 4:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

loncastuximab tesirine; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aditi Saha, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Medicine

Model Details: Sequential dose escalation based on Dose escalation guidelines.

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: August 2, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)