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Epcoritamab Plus Standard of Care Platinum-Based Chemotherapy and Autologous Hematopoietic Cell Transplant for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

ConditionsRecurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 RearrangementsRecurrent High Grade B-Cell Lymphoma With MYC and BCL6 RearrangementsRecurrent High Grade B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Nodal Marginal Zone LymphomaRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory High Grade B-Cell Lymphoma With MYC and BCL2 RearrangementsRefractory High Grade B-Cell Lymphoma With MYC and BCL6 RearrangementsRefractory High Grade B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Nodal Marginal Zone LymphomaRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, Davis

About this trial

This phase II trial tests how well epcoritamab in combination with standard of care (SOC) platinum-based chemotherapy (rituximab, ifosfamide, carboplatin, etoposide \[RICE\], rituximab, cytarabine, dexamethasone, oxaliplatin or carboplatin RDHAP/X\] or gemcitabine and oxaliplatin \[Gem/Ox\]) and autologous hematopoietic cell transplant (HCT) works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab, a type of bispecific T-cell engager, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as ifosfamide, etoposide phosphate, cytarabine, and gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. An autologous HCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving epcoritamab in combination with SOC platinum-based chemotherapy, such as RICE, RDHAP/X and Gem/Ox, and autologous HCT may kill more cancer cells in patients with relapsed or refractory LBCL.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must have histologically or cytologically confirmed R/R LBCL

Can include diffuse large B-cell lymphoma (DLBCL) (not otherwise specified [NOS] or with concurrent MYC and BCL2 rearrangements), high-grade B-cell lymphoma (HGBCL) (NOS or with MYC and BCL2 or BCL6 rearrangements) and transformed follicular lymphoma (FL) and nodal marginal zone lymphoma (MZL)

Histological confirmed CD20+ relapsed/ refractory large cell lymphoma

Must have had relapsed or refractory disease following standard frontline chemotherapy. Refractory disease is defined as large cell lymphoma not achieving complete remission, progressing, or relapsing within 6 months after first-line chemotherapy based on PET/CT per the Lugano criteria. Relapsed disease is defined as disease that recurs beyond 6 months after completion of initial chemotherapy based on PET/CT per the Lugano criteria

Disqualifiers

Any adverse event (AE) related to the previous large cell lymphoma therapy which has not recovered to grade ≤ 1 (Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) or baseline by cycle 1 day 1 (C1D1), except alopecia and non-clinically significant laboratory abnormalities

Uncontrolled intercurrent illness (including infection)

Known active central nervous system or meningeal (including leptomeningeal) involvement. Patients diagnosed with central nervous system (CNS) disease who achieved and maintained CNS complete response (CR) at the time of relapse are eligible. Lumbar puncture must be done in this case prior to study entry (within 90 days of enrollment) to demonstrate CNS CR status. Tests to investigate CNS involvement are required otherwise only if clinically indicated (i.e. disease suspected on basis of symptoms or other findings)

Receiving any other investigational treatments

Trial design

Design model

Single group

Treatments tested in this trial

  • Autologous Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Undergo autoHCT

  • Carboplatin

    Drug

    Given carboplatin

  • Cytarabine

    Drug

    Given cytarabine

  • Dexamethasone

    Drug

    Given dexamethasone

  • Epcoritamab

    Biological/Vaccine

    Given SC

  • Etoposide Phosphate

    Drug

    Given etoposide phosphate

  • Gemcitabine

    Drug

    Given gemcitabine

  • Ifosfamide

    Drug

    Given ifosfamide

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Oxaliplatin

    Drug

    Given oxaliplatin

  • Rituximab

    Biological/Vaccine

    Given rituximab

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Treatment (epcoritamab, SOC chemotherapy, autoHCT)Experimental treatment 11 interventions

Trial outcomes

Primary outcomes

1

Complete response rate (CRR)

Will be assessed by Lugano 2014. Will be calculated as the number of participants achieving complete response divided by the number of evaluable patients. CRR will be presented alongside the corresponding exact binomial 95% confidence interval.

Time frame
From first dose up to 2 years post-autologous hematopoietic cell transplantation (autoHCT) therapy

Secondary outcomes

1

Incidence of treatment-related adverse events (AEs)

The proportion of participants experiencing AEs, serious AEs, and treatment delays will be summarized. All AEs will be listed, documenting the course, outcome, severity, and relationship to the study treatment. Incidence rates of AEs and the proportion of participants prematurely withdrawn from the study due to AEs will be reported. Will be classified by severity, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Time frame
From first dose through 30 days post last epcoritamab dose
2

Progression-free survival

Will be summarized using the Kaplan-Meier method. Summary statistics will include median and event-free probabilities at pre-specified time points, along with their associated two-sided 95% confidence intervals (CIs).

Time frame
From the date of enrollment until the first occurrence of disease progression, or death from any cause, whichever occurs first, assessed up to 2 years post-autoHCT therapy
3

Objective response

Will be assessed by Lugano 2014. Will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, and efficacy parameters. For continuous variables, the number of participants, mean, median, standard deviation, minimum, and maximum values will be presented. For categorical variables, numbers and percentages of participants within each category (with a category for missing data) will be presented along with binomial exact 95% CIs, unless stated otherwise.

Time frame
From first dose up to 2 years post-autoHCT therapy
4

Overall survival

Will be summarized using the Kaplan-Meier method. Summary statistics will include median and event-free probabilities at pre-specified time points, along with their associated two-sided 95% confidence intervals.

Time frame
From first dose to death due to any causes, assessed up to 2 years post-autoHCT therapy

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, Davis

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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