Study of Epcoritamab as a Consolidation Therapy in CLL/SLL
- Conditions
- CLL/SLLCLLSLLChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaSmall Lymphocytic Lymphoma VariantChronic Lymphocytic Leukemia Variants
- Interventions
- Registration Number
- NCT07108998
- Lead Sponsor
- Zulfa Omer
- Brief Summary
This is a phase 2 study of Epcoritamab as a consolidation therapy for 2nd generation BTKi +/- Obinutuzumab in CLL/SLL patients or patients with variants of this.
- Detailed Description
This is a Phase II, multicenter trial, where we seek to test the hypothesis that administration of up to 12 cycles of epcoritamab following a 12 months or greater time period of acalabrutinib +/- obinutuzumab or zanubrutinib +/- obinutuzumab in patients who have attained a partial response or better will have a high CR conversion rate with uMRD that enables discontinuation of therapy and lead to durable remission. Additionally, Patients attaining this exceptional uMRD CR at completion of therapy will have evidence of autologous T-cell response toward the patient pre-treatment CLL cells. A safety lead in of the combination for the first 9 patients followed by Simon's 2 stage design will be implemented. Following our inclusion and exclusion criteria, eligible patients will be treated with subcutaneous epcoritamab for a total of 12 cycles while continuing their BTKi therapy. Patients will be assessed for disease response as defined by the iw-CLL 2018 response criteria following completion of cycle 6 and 12 of epcoritamab by peripheral blood labs, CT imaging and bone marrow biopsy for morphology and flow cytometry (if labs/imaging indicating CR) and MRD status through NGS assay (ClonoSEQ). MRD will be performed from bone marrow samples if BMBx is done, and if not done peripheral blood sample will be used for MRD status. All patients who complete 12 cycles of epcoritamab consolidative therapy will have the ability to continue BTKi as monotherapy regardless of MRD status, pending discussion with the patient and treating-physician.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 22
Not provided
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Obtaining a CR or nodal PR with no detectable disease in blood or bone marrow after treatment with a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab as assessed by Adaptive's NGS ClonoSEQ.
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Absence of CD20 expression on CLL cells at pre-treatment.
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Received any prior treatment ever with a CD3×CD20 bispecific antibody.
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Organ transplant recipients are excluded except those with no active graft versus host disease (GVHD) requiring treatment within 12 months of beginning treatment on study.
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Receipt of a live vaccine within 28 days prior to study treatment initiation.
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Autoimmune diseases requiring high dose immunosuppressives (e.g., above 20 mg prednisone daily).
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Central nervous system (CNS) disease(s) unless in the opinion of the investigator these would not preclude the patient from participation.
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Known hypersensitivity to any of the components of the treatment drugs (see Investigators Brochure for a list of components).
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Patients with active Richter's transformation.
a. Note: the following will be eligible and not excluded: patients with accelerated phase or prolymphocytic progression
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Patients who have received prior radiation therapy (RT) unless in the opinion of the investigator the prior receipt of RT will not adversely impact the patient's ability to participate.
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Patients who require anti-coagulation with warfarin or equivalent Vitamin K antagonist.
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Major surgery within 14 days prior to the first dose of study drug.
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Patient has significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 180 days prior to the first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or left ventricular ejection fraction ≤ 40%.
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Pregnant women, those planning to become pregnant during the study, and/or breastfeeding women are ineligible for participation.
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Patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds). No new IV therapy or intravenous antibiotics may be initiated within 2 weeks prior to first dose of study drug.
- Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HBsAg positive, or HBcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive)
- Unexplained fever > 38.3°C within 7 days prior to the first dose of study drug administration (if the fever is considered attributed to the patient's malignancy or an explained infection, the Patient may be enrolled at the discretion of the Investigator).
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Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Epcoritamab + SOC Epcoritamab Epcoritamab is the investigational product under study in combination with SOC drugs in this protocol. During C1, epcoritamab will be initiated using step-up dosing (SUD) C1D1 .16mg, C1D8 .8mg, C1D15 3 mg, C1D22 24 mg vs 48 mg (full dose) during safety lead in to determine the RP2D. On Cycles 2-3 the RP2D (24mg vs 48 mg) will be administered on Days 1, 8, 15, 22. Then Cycles 4-9 RP2D will be administered on Days 1 \& 15. Then Cycle 10-12 RP2D on Day 1 of each cycle. Epcoritamab is administered subcutaneously. The SOC BTKi are oral medications administered daily during the trial period.
- Primary Outcome Measures
Name Time Method uMRD CR as defined by negative leukemia cells to the 10^6 Post 12 cycles (approximately 336 days after the start of first cycle) of consolidative therapy with epcoritamab uMRD CR as defined by negative leukemia cells to the 10\^6 after 12 cycles of consolidative therapy with epcoritamab measured by Adaptive's NGS MRD assay (ClonoSEQ) in patients who have attained a partial response or better with detectable disease after acalabrutinib or zanubrutinib +/- obinutuzumab treatment for a minimum of 12 cycles of therapy
- Secondary Outcome Measures
Name Time Method Safety measured by CTCAE v. 5. Day 1 of Cycle 1 to 60 days after end of C12D28 (i.e., approximately 396 days after the start of intervention) Safety of epcoritamab given together with acalabrutinib or zanubrutinib in patients with CLL/SLL reported as frequency and severity of adverse events using CTCAE v. 5.
uMRD CR defined by negative leukemia cells to the 10^6 using NGG ClonoSEQ Post 6 cycles (approximately 196 days after start of intervention) of consolidation with epcoritamab. uMRD CR defined by negative leukemia cells to the 10\^6 using NGG ClonoSEQ after 6 cycles of consolidation with epcoritamab.
T-cell subsets levels measured by flow-cytometry Baseline, pre-treatment on Cycle1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 and end of Cycle 12. Each cycle is 28 days. T-cell subsets levels (include T-regulatory cells, TH17 T-cells, effector memory T-cells, central memory T-cells, naïve T-cells, and cytotoxic T-cells) at baseline, Day 1, Day 8, C2D1, C4D1, C7D1 and C12 D28 of consolidation with epcoritamab.
PFS defined as the interval between the first treatment day to the first sign of disease progression or death from any cause of patient Post 12 cycles of consolidative epcoritamab (approximately 364 days from start of intervention).. Each cycle is 28 days. PFS defined as the interval between the first treatment day to the first sign of disease progression or death from any cause after receiving 12 cycles of consolidative epcoritamab.
OS defined as time from starting treatment until death of patients Post 12 cycles of consolidative epcoritamab (approximately 364 days from start of intervention).. Each cycle is 28 days. OS defined as time from starting treatment until death of patients after receiving 12 cycles of consolidative epcoritamab.
Trial Locations
- Locations (1)
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati🇺🇸Cincinnati, Ohio, United States