Brentuximab + Chemotherapy for T-Cell Lymphoma

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive peripheral T-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, etoposide, and prednisone 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. Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma.

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.

What data supports the effectiveness of the drug Brentuximab Vedotin combined with chemotherapy for T-Cell Lymphoma?

The ECHELON-2 trial showed that Brentuximab Vedotin combined with chemotherapy (A+CHP) was effective for treating CD30-positive peripheral T-cell lymphomas, offering a promising alternative to the traditional CHOP regimen. This combination has been approved by the FDA for initial therapy, indicating its effectiveness in improving patient outcomes. ^{1 2 3 4 5}

Is Brentuximab Vedotin safe for humans?

Brentuximab Vedotin has been generally well tolerated in clinical trials for various types of lymphoma, with the most common side effect being peripheral neuropathy (nerve damage causing tingling or numbness), which often resolved completely. It has an acceptable safety profile and does not cause significant heart rhythm issues. ^{2 4 6 7 8}

How is the drug Brentuximab Vedotin with chemotherapy different from other treatments for T-cell lymphoma?

Brentuximab Vedotin combined with chemotherapy is unique because it targets CD30-positive cells, which are often present in T-cell lymphomas, and has shown better clinical responses compared to standard treatments like CHOP (a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone). This combination has been specifically approved for CD30-expressing peripheral T-cell lymphoma, offering a more targeted approach. ^{1 2 4 9 10}

Research Team

Alex F Herrera

Principal Investigator

City of Hope Comprehensive Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of brentuximab vedotin plus chemotherapy for previously untreated CD30-positive peripheral T-cell lymphoma in Canada. [2022]

2. England 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. [2022]

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

Combination of brentuximab-vedotin and ifosfamide, carboplatin, etoposide in relapsed/refractory peripheral T-cell lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy. [2023]

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

Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. [2022]

6. New Zealand 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. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. [2021]

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

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. [2021]

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

Brentuximab Beats Standard Therapies for CTCL. [2019]

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

Brentuximab Vedotin in the Treatment of Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma. [2020]