Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

Conditions

• Relapsed/Refractory Chronic Lymphocytic Leukemia
• Richter's Syndrome
• Small Lymphocytic Lymphoma
• Treatment-naïve High Risk Chronic Lymphocytic Leukemia

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Epcoritamab — BIOLOGICAL
  Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
• Epcoritamab — BIOLOGICAL
  Epcoritamab will be administered subcutaneously in cycles of 21 days and 28 days.
• rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone — DRUG
  R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.
• Venetoclax — DRUG
  Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.
• Epcoritamab — BIOLOGICAL
  Epcoritamab will be administered subcutaneously in cycles of 28 days.
• Lenalidomide — DRUG
  Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.
• Epcoritamab — BIOLOGICAL
  Epcoritamab will be administered subcutaneously in cycles of 28 days.
• Pirtobrutinib — DRUG
  Pirtobrutinib tablets will be administered in cycles of 28 days.
• Epcoritamab — BIOLOGICAL
  Epcoritamab will be administered subcutaneously in cycles of 28 days.

Study Details

The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will be tested either in Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as: * Monotherapy, or * Combination therapy: * epcoritamab + venetoclax * epcoritamab + pirtobrutinib In Non-United States (US) Participants Only: Treatment-naïve (TN) high risk (HR) (CLL): • epcoritamab + pirtobrutinib Combination therapy for Richter's Syndrome (RS): * epcoritamab + lenalidomide * epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine \[Oncovin®\] and prednisone). The study includes participants with R/R or TN HR CLL (non-US participants only)/small lymphocytic lymphoma (SLL) and participants with RS. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Participants with RS are only included in the expansion phase. Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, pirtobrutinib, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein). Study details include: * Study duration will be up to 5 years after the last participant's first treatment in the trial. * The treatment duration for each participant will be between 12 months (1 year) and 24 months (2 years), depending upon the treatment arm assigned. * The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study. All participants will receive active drug; no one will be given placebo.

Key Dates

Start date

Nov 25, 2020

Status verified

Jun 2026

Primary completion

Dec 31, 2027

Completion

Feb 29, 2028

Study Design

Enrollment

194 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Epcoritamab in R/R CLL/SLL
  In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
• Experimental: Epcoritamab in RS
  Only in expansion phase.
• Experimental: Epcoritamab + Venetoclax in R/R CLL/SLL
  In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
• Experimental: Epcoritamab + Lenalidomide in RS
  Only in expansion phase.
• Experimental: Epcoritamab + R-CHOP in RS
  Only in expansion phase.
• Experimental: Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL (Non-US Participants Only) and SLL
  Safety run-in and expansion phases.
• Experimental: Fixed Duration Epcoritamab in R/R CLL/SLL
  Only in expansion phase.

Primary Outcome Measure

Dose Escalation Phase and Safety Run-in (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days) ]

Locations (23)

Find similar trials in Birmingham, AL

Related Studies

• Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
  Recruiting · National Heart, Lung, and Blood Institute (NHLBI) · Bethesda, Maryland
• A Long-term Extension Study of PCI-32765 (Ibrutinib)
  PHASE3 · Recruiting · Janssen Research & Development, LLC · Duarte, California
• Acalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  PHASE2 · Recruiting · Mayo Clinic · Scottsdale, Arizona
• Dose-escalation and Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
  PHASE1 · Recruiting · Imugene Limited · Gilbert, Arizona