Epcoritamab (Epcor)-Containing Combination Salvage Therapy Followed by ASCT & Epcor Consolidation in Patients With Relapsed LBCL

NCT06287398 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NHL38
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate clinical efficacy of incorporating Epcoritamab into the salvage treatment routine for relapsed-refractory aggressive B-cell lymphoma, followed by autologous stem-cell transplantation (ASCT) and consolidation Epcoritamab. The main questions it aims to answer are:

• Will the addition of epcoritamab to intensive salvage chemotherapy be safe and increase the proportion of patients with relapsed or refractory (R/R) large B-cell lymphoma who achieve a complete remission prior to planned transplant?
• Is consolidation epcoritamab after ASCT deliverable and safe?
• Will consolidation epcoritamab will result in improved clearance of molecularly detectable residual disease?
• Will the combination of pre- and post-ASCT epcoritamab lead to higher rates of progression-free survival (PFS) and event free survival (EFS) at 12 months compared to historical estimates in this population. Participants will undergo three phases in this trial:
• Epcoritamab-Salvage treatment: consists of 3 cycles of R-DHAOx (rituximab, dexamethasone, cytarabine, oxaliplatin) plus Epcoritamab
• ASCT: Pre-autograft eligibility assessment for ASCT will be performed according to local practice. ASCT may be administered at local referring centre and will follow local standard operative procedures.
• Consolidation treatment: consists of six 28-day cycles of subcutaneous Epcoritamab, commencing 6 - 12 weeks post ASCT.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; DLBCL, Nos Genetic Subtypes; High Grade B-Cell Lymphoma, Not Otherwise Specified; Follicular Large Cell Lymphoma, Relapsed; Follicular Large Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  Time to event outcome measured in days from commencement of each treatment subset (salvage chemotherapy and Epcoritamab/ASCT/ Epcoritamab re-treatment) to date of first to occur out of reduced partial response (PR) after C2, commencement of non-protocolised cancer treatment, progression or death from any cause.

  12 months

Secondary Outcomes (5)

• Evaluate safety and tolerability of combination Epcoritamab with salvage-ASCT

  From enrolment to 30 days after the final treatment is completed.

• Overall response rate (ORR)

  At cycle 2 day 21 (each cycle is 28 days), cycle 3 day 21, 4 weeks post ASCT, 12 months from registration and 3-monthly during follow up (up to 24 months from registration).

• Complete response rate (CRR)

  At cycle 2 day 21 (each cycle is 28 days), cycle 3 day 21, 4 weeks post ASCT, 12 months from registration and 3-monthly during follow up (up to 24 months from registration).

• Overall Survival (OS)

  At cycle 2 day 21 (each cycle is 28 days), cycle 3 day 21, 4 weeks post ASCT, 12 months from registration and 3-monthly during follow up (up to 24 months from registration).

• Progression free survival (PFS)

  At cycle 2 day 21 (each cycle is 28 days), cycle 3 day 21, 4 weeks post ASCT, 12 months from registration and 3-monthly during follow up (up to 24 months from registration).

Study Arms (1)

Epcoritamab Treatment

EXPERIMENTAL

Single arm study - All patients undergo same treatment with Epcoritamab for salvage and consolidation phases.

Drug: Epcoritamab

Interventions

Epcoritamab DRUG

Epcoritamab (Epcor) is a bispecific antibody recognizing the T-cell antigen CD3 and the B-cell antigen CD20. Epcor is a supplied as a concentrate for solution for intended subcutaneous injection. The dose must be prepared by a qualified pharmacist using aseptic technique. Epcoritamab-Salvage treatment phase: 2-3 cycles of R-DHAOx therapy (rituximab, dexamethasone, cytarabine, oxaliplatin), given every 21 days combined with Epcoritamab subcutaneous weekly dosing (priming 0.16mg Cycle 1 Day 1, intermediate 0.8mg cycle 1 day 8, full dose 48mg from cycle 1 day 15 onwards) Epcoritamab Consolidation phase: 6 cycles (28 days each) of subcutaneous Epcoritamab, commencing between 6-12 weeks post ASCT. Epcoritamab dosing and timing for consolidation: * Cycle 1 Day 1: Priming (0.16mg) dose * Cycle 1 Day 8: intermediate (0.8mg) dose * Cycle 1 Day 15: full dose 48mg * Cycle 1 Day 22, Cycle 2-3 Days 1, 8, 15 and 22: 48mg * Cycles 4 to 6 - Days 1 and 15 (fortnightly dosing): 48mg

Epcoritamab Treatment

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older
• Confirmed diagnosis of DLBCL, Not-otherwise specified (NOS), Transformation of indolent B-cell lymphoma, High-grade B-cell lymphoma (HGBCL), NOS, Diffuse-large BCL (DLBCL)/ High-grade B-cell lymphoma (HGBL) with MYC and BCL2 rearrangements or Follicular large B-cell lymphoma according to World Health Organization (WHO) 2016 or 2022 criteria that has relapsed or progressed after one line of chemoimmunotherapy
• Transplant eligible according to local assessment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Measurable disease on computed tomography (CT) scan, defined as a nodal site greater than 1.5cm in longest axis or an extranodal site greater than 1.0cm in longest axis AND baseline fluorodeoxyglucose (FDG) positron emission tomography (PET) scans must demonstrate positive lesion compatible with CT defined anatomical tumour sites
• Histological confirmation of tumour CD20 positivity, analysed by immunohistochemistry, on a pre-enrolment tissue sample performed after most recent prior therapy
• Adequate renal function
• \- Creatinine clearance greater than 45mL per min (Cockcroft Gault formula)
• Adequate hepatic function:
• Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3x Upper Limit of Normal (ULN)
• Bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) or less than or equal to 3 if documented liver involvement and/or Gilbert's disease.
• Adequate haematologic function:
• Haemoglobin greater than or equal to 90g/L (transfusion support permitted)
• Absolute neutrophil count greater than or equal to 1.0 x 109 per L; growth factor support allowed in case of bone marrow involvement
• Platelet count greater than 75 x 109 per L or greater than or equal to 50 x 109 per L if documented marrow involvement

You may not qualify if:

• Diagnosis of primary Central Nervous System (CNS) lymphoma
• Active secondary CNS involvement of lymphoma at time of screening
• \- A prior history of secondary CNS lymphoma is allowed provided that it has been successfully treated and there are no features of recurrence.
• Prior autologous stem cell transplant
• Cervical carcinoma of Stage 1B or less.
• Non-invasive basal cell or squamous cell skin carcinoma.
• Non-invasive, superficial bladder cancer.
• Prostate cancer with a current Prostate Specific Agent (PSA) level less than 0.1 ng per mL e. indolent lymphoma
• Indolent lymphoma
• Other malignancy that has been treated with curative intent and has remained in remission for 2 years
• Any prior therapy with a bispecific antibody targeting CD3 and CD20
• Uncontrolled systemic infection
• Known HIV infection
• Known active hepatitis B or C infection based on criteria below:
• Hepatitis B virus (HBV): Patients with positive HbsAg are excluded. Patients with positive hepatitis B core antibody (antiHBc) and negative HbsAg require negative hepatitis B polymerase chain reaction (PCR) before enrolment and must be treated with antiviral therapy. Patients who are hepatitis B PCR positive will be excluded.

Sponsors & Collaborators

• Australasian Leukaemia and Lymphoma Group: lead

Study Sites (1)

Australasian Leukemia and Lymphoma Group

Melbourne, Victoria, 3121, Australia

RECRUITING

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Follicular; Recurrence

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: March 1, 2024
• Study Start: December 11, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2031
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)