Epcoritamab + GDP for Non-Hodgkin's Lymphoma

Recruiting at 3 trial locations

Overseen By Allison Lipps

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dipenkumar Modi

Must not be taking: Gemcitabine, Cisplatin, Epcoritamab

Disqualifiers: CNS involvement, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 9 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with relapsed large cell lymphoma, a type of non-Hodgkin's lymphoma. It combines chemotherapy drugs (gemcitabine, cisplatin, and dexamethasone) with a new drug, epcoritamab, administered over three cycles. After these cycles, participants may undergo additional treatments like stem cell transplants or continue with only epcoritamab if they respond well. This trial suits those who have previously received treatment for large cell lymphoma but have experienced a relapse or incomplete response. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in lymphoma care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot use any standard or experimental anti-large cell lymphoma therapy within 14 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining epcoritamab with chemotherapy drugs like gemcitabine and cisplatin is generally well-tolerated by patients with relapsed large cell lymphoma. In earlier studies, using epcoritamab with similar chemotherapy led to some expected side effects, such as cytokine release syndrome (CRS). CRS occurred in about half of the patients, but it was usually mild and did not require stopping the treatment.

Gemcitabine and cisplatin are well-known chemotherapy drugs. Patients often handle them well, but like all chemotherapy, they can cause side effects. These may include nausea, tiredness, and lower blood counts, which are common and expected with these medications.

Overall, this combination of treatments has demonstrated manageable side effects, allowing many patients to continue with their treatment plan. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Non-Hodgkin's Lymphoma because they incorporate Epcoritamab, a unique monoclonal antibody that specifically targets CD3 and CD20, potentially enhancing the immune system's ability to fight cancer cells. Unlike traditional chemotherapy, which can affect healthy cells, Epcoritamab provides a more targeted approach, potentially reducing side effects. Additionally, the combination with GDP (Gemcitabine, Cisplatin, and Dexamethasone) and options for maintenance with Epcoritamab or advanced therapies like CAR T-cell therapy could offer more personalized and effective treatment strategies. This approach aims to improve outcomes for patients who have limited options with current standard treatments.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

In this trial, participants will receive a combination of epcoritamab with gemcitabine, cisplatin, and dexamethasone (known as GDP) to treat relapsed large cell lymphoma. Epcoritamab is a specialized antibody that helps the immune system target and destroy cancer cells by focusing on specific proteins called CD3 and CD20. Research has shown that epcoritamab, when combined with GDP, may be promising for treating certain types of non-Hodgkin’s lymphoma, especially when other treatments have failed. The trial aims to determine whether combining epcoritamab with GDP can enhance effectiveness, as these drugs are known to work well together against lymphoma cells. Overall, evidence suggests that this treatment combination could be effective for people with relapsed large cell lymphoma. ^{1 4 5 6 7}

Who Is on the Research Team?

Dipenkumar Modi, MD

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

Adults over 18 with CD20+ relapsed large cell lymphoma, who've had at least one prior systemic therapy and are eligible for high dose chemotherapy and stem cell transplant. They must have measurable disease, adequate organ function, a life expectancy of more than 6 months, and agree to use contraception. HIV-positive patients can join if treated; those with hepatitis B or C must meet specific criteria.

Inclusion Criteria

I can understand and follow the study's procedures for its duration.

My lymphoma has returned and tests show it is CD20 positive.

I have been mostly active and able to care for myself in the last 28 days.

Exclusion Criteria

I have moderate to severe nerve pain or numbness.

I do not have any current infections or significant infections in the last 2 weeks.

Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, or being compliant with the study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 cycles of combination therapy consisting of GDP and epcoritamab. Each cycle lasts 21 days.

9 weeks

3 visits per cycle (in-person)

Radiology Imaging

Patients undergo radiology imaging for disease assessment after completion of Cycle 3.

1 week

Epcoritamab Monotherapy

Epcoritamab monotherapy is offered to selected subjects who become ineligible for SCT or CAR T-cell therapy, starting 2 weeks after Cycle 3 Day 15.

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Epcoritamab
• Gemcitabine

Trial Overview

The trial tests Epcoritamab combined with GDP (gemcitabine, dexamethasone, cisplatin) chemotherapy in three cycles for treating relapsed large cell lymphoma. Afterward, patients may receive autoSCT/CAR T-cell therapy or continue epcoritamab alone based on the doctor's discretion.

How Is the Trial Designed?

Group I: GDP + Epcoritamab + Epcoritamab Maintenance Experimental Treatment 2 Interventions

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15 of each Cycle. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritabab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8 of each Cycle. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1 of each Cycle. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4 of Cycle 1 ONLY. Dexamethasone Days 1-4: 40mg Cycles 4-9 (Cycle =28 Days) Epcoritamab will be administered by subcutaneous injection on Days 1, 8, and 15 of Cycles 4-9.

Group II: GDP + Epcoritamab + AutoSCT or CAR T-cell therapy Experimental Treatment 3 Interventions

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritamab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4. Dexamethasone Days 1-4: 40mg After completion of Cycle 3 Autologous stem cell transplant (AutoSCT) OR CAR T-cell therapy

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Dipenkumar Modi

Lead Sponsor

Trials

1

Recruited

30+

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Published Research Related to This Trial

The combination of carboplatin and cyclophosphamide is emerging as the preferred treatment for epithelial ovarian cancer due to its effectiveness and lower toxicity compared to cisplatin plus cyclophosphamide, based on several prospective studies.

Current clinical trials are exploring high-dose carboplatin regimens and combinations with other treatments, showing promise in improving survival rates for patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent advances in ovarian cancer chemotherapy]. Hatae, M., Onishi, Y., Kume, H., et al.[2018]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Cis-dichlorodiammineplatinum(II) can cause serious side effects such as nephrotoxicity, gastrointestinal issues (like nausea and vomiting), and myelosuppression, highlighting the need for careful monitoring during treatment.

Other potential side effects include ototoxicity (which can lead to hearing loss), anaphylactic reactions, and peripheral neuropathies, indicating that while the drug may be effective, its safety profile requires close attention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic effects of cis-dichlorodiammineplatinum(II) in man. Von Hoff, DD., Schilsky, R., Reichert, CM., et al.[2022]

A phase II trial of cisdiammino-dichloro platinum (CDDP) showed significant effectiveness against testis embryonic carcinoma, ovarian carcinoma, and epidermoid cancers, particularly in head and neck and cervical cancers.

While CDDP demonstrates strong anti-cancer activity, it is associated with notable toxicity primarily affecting the digestive and renal systems, leading to its use in combination therapies for the indicated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. Hayat, M., Bayssas, M., Brulé, G., et al.[2013]

In a phase II study, cis-dichlorodiammineplatinum(II) (CDDP) demonstrated activity as a single agent in treating non-Hodgkin's lymphoma, with 3 out of 10 patients achieving partial remission lasting 7-15 weeks.

The combination of CDDP with ICRF-159 was not effective, as none of the 8 patients treated with this combination achieved an objective response, indicating it may not be a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

cis-dichlorodiammineplatinum(II) with and without ICRF-159 in non-Hodgkin's lymphoma. Corder, MP., Wiesenfeld, M., Maguire, LC., et al.[2013]

In a study involving 25 patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma, cis-dichlorodiammineplatinum(II) showed limited efficacy, resulting in one complete response and two partial responses, indicating it may have some therapeutic potential.

The treatment was associated with significant myelosuppression, particularly leukopenia and thrombocytopenia, which were more severe than in previous studies, likely due to the patients' extensive prior treatments and the presence of tumor-bearing marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. Rossof, AH., Coltman, CA., Jones, SE., et al.[2013]

In a Phase II study involving 77 patients with urologic malignancies, cis-diaminedichloroplatinum(II) (CIS-DDP) demonstrated significant efficacy, with overall response rates of 73.3% for testicular tumors and 50.0% for bladder tumors, indicating its potential as an effective treatment option.

However, the treatment was associated with considerable adverse effects, including gastrointestinal issues in 78.5% of patients, as well as myelosuppression and renal dysfunction, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study on cis-diamminedichloroplatinum (II) by a collaborative study]. [2013]

CI-973 shows promising efficacy in preclinical models, demonstrating activity comparable or superior to cisplatin and carboplatin, and is effective against cisplatin-resistant cancer cell lines.

In a phase I trial with 28 patients, CI-973 exhibited a favorable safety profile with no renal or auditory toxicity, although mild to moderate nausea and vomiting were common; the maximum tolerated dose was determined to be 290 mg/m2 for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. Theriault, RL., Cohen, IA., Esparza, L., et al.[2019]

In a study of 69 patients with relapsed and refractory Hodgkin and Non-Hodgkin lymphoma, the GDP/R-GDP regimen effectively mobilized CD34+ stem cells in 98% of chemosensitive patients, allowing them to proceed to autologous stem cell transplantation.

The treatment demonstrated low toxicity, making it suitable for outpatient settings, and was particularly effective in patients with early-stage disease, suggesting its potential as a preferred option for stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience Batgi, H., Başcı, S., Dal, MS., et al.[2022]

In a study involving 557 patients with advanced non-small-cell lung cancer (NSCLC), the combination of cisplatin and gemcitabine (CG) showed significantly better response rates compared to nonplatinum sequential doublets, with response rates of 42% for CG versus 27% for GV-VI.

While the triplet regimen (CGV) had higher toxicity rates, including increased instances of severe neutropenia and thrombocytopenia, the median survival and time to progression were similar across all treatment groups, supporting CG as a standard first-line treatment for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. Alberola, V., Camps, C., Provencio, M., et al.[2022]

Cis-diamminedichloroplatinum(II) (cis-DDP) is a highly effective antineoplastic agent, particularly against non-seminomatous testicular cancer, bladder cancer, and head and neck tumors, with mild myelosuppression allowing for combination therapies.

Despite its potential for nephrotoxicity, this side effect can be managed through forced diuresis, making cis-DDP a viable option for combination chemotherapy in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]. Osieka, R., Schmidt, CG.[2019]

Cis-diamminedichloroplatinum (DDP) has shown strong efficacy against germinal tumors of the testis and promising results in various epithelial cancers, including ovarian and bladder cancers, based on renewed clinical interest and research.

Recent advancements, such as induced diuresis to reduce nephrotoxicity and the identification of safer dosing strategies, suggest that DDP could have a significant future role in cancer treatment, although further investigation into its clinical potential and mechanisms of action is still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum complexes in cancer chemotherapy. [2013]

The GDP regimen (gemcitabine, dexamethasone, and cisplatin) demonstrated a 58.3% overall response rate in 24 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, indicating its efficacy as a salvage treatment.

The treatment was relatively well-tolerated, with no treatment-related deaths and mild non-hematologic toxicities, although 37.5% of patients experienced severe leucopenia, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive non-Hodgkin's Lymphoma: a report of 24 cases]. Fan, Y., Huang, ZY., Luo, LH., et al.[2015]

The combination of gemcitabine, dexamethasone, and cisplatin (GDP) showed a promising overall response rate of 49% in patients with recurrent or refractory non-Hodgkin lymphoma, with 16% achieving complete responses after two treatment cycles.

Despite some significant toxicities, such as grade 3 and 4 neutropenia in 33% and 39% of patients respectively, the GDP regimen can be safely administered to outpatients, allowing many patients to proceed to stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Crump, M., Baetz, T., Couban, S., et al.[2022]

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The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...