Brentuximab + Chemotherapy for T-Cell Lymphoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Prior PTCL treatment, Cardiac disease, CNS involvement, 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

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

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of brentuximab vedotin combined with chemotherapy in treating CD30-positive peripheral T-cell lymphoma. Brentuximab vedotin, a targeted therapy, attaches to cancer cells and delivers a toxic agent to kill them, while chemotherapy stops cancer cells from growing or spreading. Individuals with this type of lymphoma who have not received extensive prior treatments might be suitable for the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get a clear answer based on your specific situation.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that brentuximab vedotin yields promising results in treating various lymphomas. One study found that this treatment helped shrink tumors in many patients with relapsed or hard-to-treat CD30-positive lymphomas. However, previous studies noted some unwanted side effects, including two treatment-related deaths. This indicates that while the drug can be effective, it also carries some risks.

The chemotherapy combination of etoposide, doxorubicin, cyclophosphamide, and prednisone is known for its potency. Reports indicate it can significantly damage blood cells, a common side effect of these drugs. Despite this, many patients have experienced positive treatment outcomes.

In summary, both brentuximab vedotin and the chemotherapy combination have demonstrated effectiveness but also come with serious side effects. Participants in clinical trials should consider these potential risks and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for T-cell lymphoma?

Brentuximab Vedotin is unique because it targets a specific protein called CD30 on the surface of cancer cells in T-cell lymphoma, delivering a powerful anti-cancer drug directly to the tumor. This targeted approach can potentially reduce harm to healthy cells compared to traditional chemotherapy, which often affects both cancerous and healthy cells alike. Researchers are excited about this treatment because it combines the precision of Brentuximab Vedotin with the proven effectiveness of chemotherapy drugs like cyclophosphamide, doxorubicin, and etoposide, aiming to improve outcomes for patients with T-cell lymphoma.

What evidence suggests that brentuximab vedotin and combination chemotherapy might be an effective treatment for T-cell lymphoma?

Studies have shown that brentuximab vedotin can shrink tumors and provide lasting benefits for many patients with CD30-positive lymphomas. Research indicates that it works by delivering a toxic substance directly to cancer cells, effectively killing them. In this trial, participants will receive a combination of brentuximab vedotin with chemotherapy drugs, including etoposide, doxorubicin, cyclophosphamide, and prednisone. Adding etoposide to the CHOP regimen (a combination of these drugs) has produced promising results in treating aggressive lymphomas, including T-cell types. These treatments help stop cancer cells from growing and spreading. Together, brentuximab vedotin and this combination chemotherapy show potential for effectively treating CD30-positive peripheral T-cell lymphoma. ^{3 5 6 7 8}

Who Is on the Research Team?

Alex F Herrera

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with CD30-positive peripheral T-cell lymphoma. Participants must have measurable disease, proper liver and kidney function, a certain level of blood cells, and no severe infections or other cancers in remission less than 3 years. Pregnant or breastfeeding women can't join, nor those with HIV or hepatitis B/C. Patients should not have had previous systemic anti-lymphoma treatments except possibly one cycle of specific therapies.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My condition is PTCL-NOS.

I have been diagnosed with Angioimmunoblastic T-cell lymphoma.

Exclusion Criteria

I have had progressive multifocal leukoencephalopathy in the past.

I have been treated for PTCL with medications, experimental drugs, or radiation.

I may have had one round of specific cancer treatments but started the study treatment after 19 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive cyclophosphamide, doxorubicin, etoposide, prednisone, and brentuximab vedotin as induction therapy

18 weeks

6 cycles, every 21 days

Consolidation

Patients receive brentuximab vedotin post-consolidative therapy or after completing induction

30 weeks

10 cycles, every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

3 visits (at 30 days, 6 months, and 12 months)

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Etoposide Phosphate, Doxorubicin Hydrochloride, Cyclophosphamide, Prednisone

Trial Overview The trial tests brentuximab vedotin combined with chemotherapy drugs (cyclophosphamide, doxorubicin, etoposide phosphate, prednisone) against this type of lymphoma. Brentuximab vedotin targets cancer cells by attaching to CD30 and delivering a toxin to kill them while the chemo drugs work to stop cancer growth in various ways.

How Is the Trial Designed?

Group I: Treatment (CHEP-BV) Experimental Treatment 8 Interventions

INDUCTION: Patients receive cyclophosphamide IV and doxorubicin IV on day 1, etoposide IV on days 1-3, and prednisone PO on days 1-5. Patients also receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (or for up to 5 cycles for patients who received 1 cycle of CHOP-like or CHP-BV therapy prior to induction, per investigator's discretion) in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy, post-consolidative radiation therapy, or after completing induction cycle 6 (cycle 5 for patients who qualify for receiving 5 cycles of CHEP-BV instead of 6), patients with objective response (complete response or partial response) receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Brentuximab vedotin demonstrated a high overall objective response rate of 75% in 102 patients with relapsed Hodgkin lymphoma and 86% in 58 patients with relapsed systemic anaplastic large cell lymphoma, indicating its efficacy as a targeted treatment.

The treatment was generally well tolerated, with peripheral neuropathy being the most common side effect; however, about half of the patients who experienced this side effect saw complete resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Garnock-Jones, KP.[2021]

In a retrospective case series of 13 patients with Sézary syndrome, brentuximab vedotin demonstrated a global response rate of 38%, with notable efficacy in blood (63% response) and lymph nodes (50% response), suggesting it may be a viable treatment option for this challenging condition.

The treatment was generally well-tolerated, with manageable side effects such as peripheral neuropathy, which resolved in some cases, indicating that brentuximab vedotin could provide a safer alternative for patients with refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. Lewis, DJ., Haun, PL., Samimi, SS., et al.[2021]

Brentuximab vedotin, an antibody-drug conjugate, does not cause significant prolongation of the QT/QTc interval, indicating a favorable cardiac safety profile in patients with CD30-positive hematologic malignancies.

In a phase 1 study involving 52 patients, brentuximab vedotin was well tolerated, with no clinically meaningful changes in cardiac repolarization and a response rate consistent with previous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. Han, TH., Chen, R., Advani, R., et al.[2021]

The ECHELON-2 trial demonstrated that the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone (A+CHP) significantly improved progression-free survival in patients with CD30-positive peripheral T-cell lymphomas, with a median of 48.2 months compared to 20.8 months for the standard CHOP regimen.

The safety profile of A+CHP was manageable, with similar rates of adverse events like febrile neutropenia and peripheral neuropathy compared to CHOP, indicating that A+CHP is a viable and effective front-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Horwitz, S., O'Connor, OA., Pro, B., et al.[2022]

In a study of 1344 patients with peripheral T-cell lymphoma (PTCL), those treated with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A + CHP) had a lower rate of subsequent therapy compared to those treated with CHOP, indicating potentially better initial treatment efficacy.

The study highlighted that patients in the real-world setting were older and had more comorbidities than those in clinical trials, emphasizing the need for retrospective analyses to understand the impact of new treatments in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy. Burke, JM., Liu, N., Yu, KS., et al.[2023]

In the international phase III ALCANZA trial, brentuximab vedotin, a CD30-directed antibody-drug conjugate, showed significantly better clinical responses in patients with cutaneous T-cell lymphomas compared to standard treatments like methotrexate or bexarotene.

This study highlights the efficacy of brentuximab vedotin as a more effective treatment option for patients with this type of lymphoma, suggesting a promising advancement in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Beats Standard Therapies for CTCL. [2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5746164/

Five-year results of brentuximab vedotin in patients with ... An estimated 91% of patients who experienced peripheral neuropathy with brentuximab vedotin reported resolution or improvement of symptoms. Abstract. This ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7069

Results from the phase 2 SGN35-032 study. There were 2 (3%) treatment-related deaths: 1 pt died of decreased appetite and 1 pt died of general physical health deterioration. Conclusions: ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4438/529456/Final-Results-of-a-Phase-II-Study-of-Brentuximab

Final Results of a Phase II Study of Brentuximab Vedotin and ... Five patients achieved complete response (2 CTCL, 3 PTCL), four achieved partial response (3 CTCL, 1 PTCL), and ten had stable disease (all CTCL) ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1002965

Brentuximab Vedotin (SGN-35) for Relapsed CD30- ... Brentuximab vedotin induced durable objective responses and resulted in tumor regression for most patients with relapsed or refractory CD30-positive lymphomas.

5. takedaoncology.com takedaoncology.com/news/news-releases/back-view-printer-friendly-version-takeda-and-seattle-genetics-announce-positive-data-from-phase-3-alcanza-clinical-trial-of-adcetris-brentuximab-vedotin-for-cd30-expressing-cutaneous-t-cell-lymphoma/

Takeda and Seattle Genetics Announce Positive Data from ... The results of the ALCANZA trial demonstrated that treatment with ADCETRIS resulted in a highly statistically significant improvement in the ORR4 versus the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3499340/

Brentuximab vedotin - PMC At least PR was achieved in 54% (CR in 29%) of the Hodgkin lymphoma patients and in 4 out of 5 patients with ALCL (all CR). The patient with peripheral T cell ...

7. adcetrispro.com adcetrispro.com/classical-hodgkin-lymphoma-post-auto-hsct-consolidation/efficacy

ADCETRIS® (brentuximab vedotin) Efficacy Data - Safety Info Brentuximab vedotin (ADCETRIS) is recommended by the NCCN Guidelines as a Category 2A treatment option for 1 year of post-auto-HSCT consolidation treatment.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3731651/

Safety and efficacy of brentuximab vedotin for Hodgkin ... The estimated 12-month survival was 89% and the median progression-free survival (PFS) was 5.6 months. Adverse events associated with brentuximab vedotin were ...