Brentuximab Vedotin + R-CHP for Non-Hodgkin's Lymphoma

(BV mini CHP Trial)

Not currently recruiting at 1 trial location

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Patrick Reagan

Must not be taking: Investigational drugs

Disqualifiers: Low platelets, Low neutrophils, Dialysis, Heart failure, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to treat Diffuse Large B-Cell Lymphoma (DLBCL), a type of non-Hodgkin's lymphoma. The study adds brentuximab vedotin (also known as Adcetris, an antibody-drug conjugate) to the usual R-CHP chemotherapy, aiming to improve treatment outcomes for elderly patients. It targets those aged 75 and older, diagnosed with DLBCL, who have not received previous anthracycline-based treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in DLBCL care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients should not have received certain treatments like anthracycline-containing regimens before. It's best to discuss your current medications with the trial team.

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

Research has shown that the combination of brentuximab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) has been studied before. In these studies, most patients tolerated the treatment well. However, like any medication, some side effects occurred, including low blood cell counts and tiredness, which are common with cancer treatments.

Brentuximab vedotin is already FDA-approved for other types of lymphomas, indicating that its safety is fairly well understood. While the combination with R-CHP is still under investigation for this specific condition, using these drugs separately has been manageable for many patients.

Prospective trial participants should consult a doctor to understand potential side effects and their management. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Brentuximab Vedotin with R-CHP for treating Non-Hodgkin's Lymphoma because it introduces a novel mechanism of action. Unlike the standard R-CHOP regimen, which is the current go-to approach, Brentuximab Vedotin uniquely targets the CD30 protein on cancer cells, delivering a potent anti-cancer agent directly to these cells. This targeted approach has the potential to reduce side effects while boosting effectiveness, offering new hope for better patient outcomes.

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

Research has shown that combining brentuximab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) may effectively treat certain types of non-Hodgkin lymphoma. In this trial, participants will receive this combination, labeled as BV+mini-R-CHP, to evaluate its safety and effectiveness for older patients, who often have fewer treatment options. Previous studies have found that using rituximab with similar drugs leads to high rates of patients remaining free from major problems after treatment, with about 80% of patients doing well. Brentuximab vedotin has already succeeded in treating Hodgkin lymphoma and other similar conditions. Early research suggests that this new combination could work by specifically targeting cancer cells, potentially improving results for patients with diffuse large B-cell lymphoma (DLBCL). ^{1 3 4 5 6}

Who Is on the Research Team?

Patrick M Reagan, MD

Principal Investigator

Wilmot Cancer Institute, University of Rochester Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women aged 75 or older with a specific type of blood cancer called DLBCL. They must be able to consent, have an ECOG performance status of 0-3, no prior therapy for their condition (except possibly prednisone), and adequate liver function. People with certain other health conditions or treatments are excluded.

Inclusion Criteria

My lymphoma has both slow-growing and aggressive features.

I understand the study details and am willing to sign the consent form.

I have not had treatment for DLBCL or HT, except possibly a short course of prednisone.

Exclusion Criteria

HIV positive

I am currently on dialysis.

My heart's pumping ability is significantly reduced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone for six cycles

20 weeks

6 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Cyclophosphamide
• Doxorubicin
• Prednisone
• Rituximab

Trial Overview The study tests a combination of drugs: brentuximab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone in elderly patients with DLBCL. It modifies the standard R-CHOP regimen by omitting vincristine due to its overlapping toxicities with brentuximab vedotin.

How Is the Trial Designed?

Group I: BV+mini-R-CHP Experimental Treatment 5 Interventions

Brentuximab vedotin 1.8 mg/kg IV day 1 for six cycles Rituximab 375 mg/m2 IV day 1 for six cycles Cyclophosphamide 400 mg/m2 IV day 1for six cycles Doxorubicin 25 mg/m2 IV day 1 for six cycles Prednisone 40 mg/m1 PO days 1-5 for six cycles

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Patrick Reagan

Lead Sponsor

Trials

1

Recruited

20+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

In a study of 134 patients with diffuse large B-cell lymphoma (DLBCL) involving the testis, the addition of rituximab to standard chemotherapy (R-CHOP) significantly improved progression-free survival and overall survival, with hazard ratios of 0.42 and 0.39 respectively, indicating a strong protective effect.

Despite the benefits of rituximab in reducing lymphoma recurrence, the risk of central nervous system (CNS) relapse remained high, suggesting that additional strategies for CNS prophylaxis are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. Kridel, R., Telio, D., Villa, D., et al.[2017]

Rituximab plus bendamustine (R-B) is less toxic and achieves similar complete remission rates compared to R-CHOP in patients with follicular lymphoma grade 3A, with 97% vs. 96% complete remissions respectively.

Patients treated with R-B experienced significantly lower relapse rates (16% vs. 41%) and longer progression-free survival (15 years vs. 11.7 years) compared to those treated with R-CHOP, making R-B a more effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. Mondello, P., Steiner, N., Willenbacher, W., et al.[2019]

In a study of 112 patients under 65 years old with diffuse large B-cell lymphoma, the combination of rituximab and high-dose sequential chemotherapy led to an impressive 80% clinical remission rate, demonstrating its efficacy in treating this aggressive cancer.

At a median follow-up of 48 months, 78% of patients remained alive and 73% were in continuous remission, indicating that this treatment significantly improves life expectancy compared to conventional chemotherapy for younger patients with higher risk scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Tarella, C., Zanni, M., Di Nicola, M., et al.[2022]

Paclitaxel and docetaxel are effective antineoplastic drugs that work by promoting microtubule assembly and inhibiting disassembly, showing clinical activity against ovarian, breast, and bronchial cancers.

Both drugs can cause dose-limiting neutropenia and other side effects like myalgias and alopecia, but premedications have been effective in reducing hypersensitivity reactions, allowing for safer administration in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere). Pazdur, R., Kudelka, AP., Kavanagh, JJ., et al.[2019]

The combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) shows high efficacy in treating metastatic breast cancer, with response rates reaching up to 80% in preliminary phase II trials.

The TAC regimen is well tolerated, with low rates of cardiac toxicity (only 2% experienced reversible congestive heart failure) despite the high incidence of grade 4 neutropenia in 68% of treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Nabholtz, JM., Smylie, M., Mackey, JR., et al.[2018]

In a study of seven patients with non-Hodgkin lymphoma treated with rituximab (RTX) and chemotherapy, there was a significant reduction in their ability to mount an immune response to vaccines, indicating increased susceptibility to infections.

The introduction of intravenous immunoglobulin (IVIg) therapy was crucial for managing recurrent infections, such as pneumonia and sinusitis, highlighting the importance of monitoring and addressing hypogammaglobulinemia in patients undergoing RTX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. de Souza, KJ., Ferro, RS., Prestes-Carneiro, LE., et al.[2019]

In a study of 80 patients with high-risk diffuse large B cell lymphoma (DLBCL), the DA.R-EPOCH treatment showed comparable progression-free and overall survival rates to the standard R-CHOP treatment, indicating similar efficacy.

However, DA.R-EPOCH was associated with significantly higher treatment costs, averaging around USD 106,940 compared to USD 58,509 for R-CHOP, highlighting a trade-off between cost and treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost Analysis of R-CHOP Versus Dose-Adjusted R-EPOCH in Treatment of Diffuse Large B-Cell Lymphoma with High-Risk Features. Dholaria, B., Vanegas, YAM., Diehl, N., et al.[2021]

Docetaxel and doxorubicin combinations (TA or TAC) show high efficacy in treating metastatic breast cancer, with response rates between 70% to 80%, even in patients with visceral metastases.

The main toxicity observed is neutropenia, but significant cardiotoxicity has not been reported, even at high cumulative doses of doxorubicin, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. Nabholtz, JM., Smylie, M., Mackey, J., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8168499/

Brentuximab vedotin in combination with rituximab ... Rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) results in event-free survival rates of about 80% when followed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02734771

A Study of Brentuximab Vedotin, Rituximab, and Dose ... This is a study incorporating brentuximab vedotin and dose attenuated rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) into initial therapy ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/3738/Brentuximab-Vedotin-Plus-R-CHP-a-Frontline

Brentuximab Vedotin Plus R-CHP a Frontline Treatment ... The CD30-directed immunoconjugate brentuximab vedotin has demonstrated efficacy in Hodgkin lymphoma (HL) and other T-cell lymphomas.

4. adcetrispro.com adcetrispro.com/previously-untreated-salcl-cd30-expressing-ptcl/efficacy

Efficacy - ADCETRIS® (brentuximab vedotin)+CHP “It was really interesting to see the data and the positive results across different subtypes of PTCL, progression-free survival benefit, and even overall ...

5. es.aetna.com es.aetna.com/cpb/medical/data/800_899/0823.html

Brentuximab Vedotin (Adcetris) - Medical Clinical Policy ... The requested drug will be used in combination with cyclophosphamide, doxorubicin, and prednisone (CHP);. T-Cell lymphomas (a type of non-Hodgkin lymphoma). For ...

6. researchgate.net researchgate.net/publication/384533763_Brentuximab_vedotin_in_combination_with_rituximab_cyclophosphamide_doxorubicin_and_prednisone_as_frontline_treatment_for_patients_with_CD30-positive_B-cell_lymphomas

(PDF) Brentuximab vedotin in combination with rituximab, ... We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, ...