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

(BV mini CHP Trial)

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

24 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Brentuximab Vedotin + R-CHP for Non-Hodgkin's Lymphoma?

The research indicates that rituximab, a component of the R-CHP regimen, is widely used and effective as a first-line therapy for B cell lymphoma, which is a type of Non-Hodgkin's Lymphoma. Additionally, R-CHOP, a similar regimen to R-CHP, has shown comparable clinical outcomes in treating high-risk diffuse large B-cell lymphoma. ^{1 2 3 4 5}

What safety data exists for the combination of Brentuximab Vedotin, Cyclophosphamide, Doxorubicin, Prednisone, and Rituximab in humans?

The combination of docetaxel, doxorubicin, and cyclophosphamide has been studied in breast cancer, showing that while it is effective, it can cause significant side effects like neutropenia (low white blood cell count), febrile neutropenia (fever with low white blood cell count), and infections. Cardiac toxicity was rare, but one case of reversible heart failure was reported. These findings suggest that while the treatment can be effective, it comes with notable risks that need to be managed. ^{6 7 8 9 10}

What makes the drug Brentuximab Vedotin + R-CHP unique for treating Non-Hodgkin's Lymphoma?

Brentuximab Vedotin + R-CHP is unique because it combines a targeted therapy (Brentuximab Vedotin) with a modified version of the R-CHOP regimen, replacing vincristine with Brentuximab Vedotin. This combination aims to enhance the treatment's effectiveness by specifically targeting cancer cells while maintaining the benefits of the established R-CHOP regimen. ^{2 11 12 13 14}

What is the purpose of this trial?

This is a study incorporating brentuximab vedotin and dose attenuated rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) into initial therapy for elderly patients with DLBCL. Vincristine will be omitted from the standard R-CHOP regimen given the overlapping toxicities with brentuximab vedotin.

Research Team

Patrick M Reagan, MD

Principal Investigator

Wilmot Cancer Institute, University of Rochester Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Differences in Quality of Life Between Bendamustine-Rituximab and R-CHOP/R-CVP in Patients With Previously Untreated Advanced Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma. [2016]

2. England 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). [2022]

3. England pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. [2019]

4. England 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Outcome of Patients With Non-Hodgkin Lymphomas With Concurrent MYC and BCL2 Rearrangements Treated With CODOX-M/IVAC With Rituximab Followed by Hematopoietic Stem Cell Transplantation. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere). [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Dose-dense nonpegylated liposomal Doxorubicin and docetaxel combination in breast cancer: dose-finding study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. [2017]

12. Japan 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]. [2015]

13. England 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. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Upfront autologous stem cell transplantation for untreated high-risk diffuse large B-cell lymphoma in patients up to 60 years of age. [2015]