Brentuximab Vedotin + CHEP for Adult T-Cell Leukemia/Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Jana Hall

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Ketoconazole, Itraconazole, Ritonavir, others

Disqualifiers: Pregnancy, Active malignancy, Cardiac disease, 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: 3

Duration: 6-18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for adult T-cell leukemia/lymphoma (ATLL), a rare cancer type. The study aims to evaluate patient responses to a combination of brentuximab vedotin (also known as Adcetris, SGN-35, or cAC10-vcMMAE) and a standard chemotherapy mix called CHEP. This treatment is not yet approved for ATLL, so researchers are exploring its effectiveness, particularly concerning a marker called CD30 on cancer cells. The trial suits those diagnosed with ATLL, who have had limited prior treatment, and whose cancer cells express the CD30 marker. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude patients taking certain medications like ketoconazole, itraconazole, and others listed in the patient handout. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that brentuximab vedotin, when combined with other chemotherapy drugs, generally has a manageable safety profile for patients with T-cell lymphomas. Serious side effects, such as pneumonia and fever, have been reported but are uncommon, affecting about 4% of patients. Other side effects, like nausea and vomiting, occur in 2-3% of cases.

In another study, brentuximab vedotin was combined with cyclophosphamide, doxorubicin, etoposide, and prednisone, a treatment known as BV-CHEP. The results were positive for patients with CD30-positive T-cell lymphomas, with some achieving remission.

The treatment's safety is supported by its FDA approval for other types of lymphomas, indicating it has been tested in many patients and found safe for those conditions. However, the use of etoposide in this study is new, and researchers believe it will improve patient outcomes.

Prospective trial participants should consider that while the treatment is generally well-tolerated, there are risks of side effects, as with any cancer treatment. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Brentuximab Vedotin (BV) and CHEP for treating Adult T-Cell Leukemia/Lymphoma (ATLL) because it targets CD30-positive cancer cells, which are commonly found in ATLL. Unlike standard treatments that primarily rely on chemotherapy regimens, Brentuximab Vedotin is an antibody-drug conjugate, providing a more targeted approach by delivering chemotherapy directly to cancer cells, potentially reducing damage to healthy cells. This targeted mechanism could lead to more effective treatments with fewer side effects, offering new hope for patients with this challenging condition.

What evidence suggests that this treatment might be an effective treatment for ATLL?

Research shows that a treatment combining brentuximab vedotin with other chemotherapy drugs, such as cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP), holds promise for aggressive adult T-cell leukemia/lymphoma (ATLL). Participants in this trial will receive the BV-CHEP combination. Previous studies have demonstrated that brentuximab vedotin, when used with similar chemotherapy drugs, resulted in complete responses in patients with T-cell lymphomas, including ATLL, meaning the cancer was no longer detectable after treatment. High overall response rates and complete remission rates support the effectiveness of this combination. Adding etoposide is expected to further improve outcomes, as it has proven helpful in treating other types of T-cell lymphomas. ^{5 6 7 8 9}

Who Is on the Research Team?

Dittus Christopher, DO, MPH

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific type of cancer called Adult T-cell leukemia/lymphoma (ATLL), who have not been treated or have had only one round of chemotherapy. They must test negative for HIV, show adequate organ function, and if they can bear children, agree to use effective contraception methods. People with severe liver or kidney problems, active brain lymphoma lesions, certain other cancers, allergies to the study drugs or components, taking prohibited medications, previous brentuximab vedotin treatment, significant neuropathy or symptomatic heart disease are excluded.

Inclusion Criteria

Informed consent and HIPAA authorization for release of personal health information obtained

Documented negative serologic testing for human immunodeficiency virus (HIV)

Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 24 weeks (6 months) after treatment discontinuation

Exclusion Criteria

I have been treated with brentuximab vedotin before.

I have heart problems that cause symptoms.

Patients receiving prohibited medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BV-CHEP therapy for 2-6 cycles, each cycle lasting 21 days, with PET/CT scans to assess disease progression

6-18 weeks

1 visit every 21 days for each cycle

Maintenance

Participants who are not eligible for a bone marrow transplant and have CD30-positive ATLL may continue on brentuximab vedotin alone until disease progression

Until disease progression

1 visit every 21 days

Follow-up

Participants are monitored for survival and disease progression with PET/CT or CT scans and blood tests every 6 months for 2 years, and followed for survival for up to 5 years

5 years

1 visit every 6 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• CHEP

Trial Overview The trial tests an investigational treatment named BV-CHEP which combines brentuximab vedotin (an FDA-approved drug for some lymphomas) with standard chemotherapy drugs cyclophosphamide, doxorubicin, etoposide and prednisone. The aim is to see if this combination works better in patients whose ATLL cells express CD30 protein markers.

How Is the Trial Designed?

Group I: Open-label, Multicenter, Single-Arm Experimental Treatment 2 Interventions

This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP \[(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m\^2 on D1; doxorubicin 50 mg/m\^2 on D1, etoposide 100 mg/m\^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)\] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

Brentuximab vedotin, an antibody-drug conjugate used for treating certain lymphomas, showed improved progression-free survival in patients with cutaneous T-cell lymphoma (CTCL) without a direct correlation to the drug's exposure levels, indicating its efficacy is consistent across different exposure ranges.

The study found that while higher exposure to the drug was linked to an increase in severe treatment-emergent adverse events (TEAEs), the results support the use of a standard dose of 1.8 mg/kg every 3 weeks, with the option for dose reductions in patients experiencing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. Suri, A., Mould, DR., Liu, Y., et al.[2019]

A phase 2 study demonstrated promising efficacy of brentuximab vedotin, an antibody-drug conjugate, in treating patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The results suggest that BV could be a valuable treatment option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time has come for immunotherapy in PTCL. Bachy, E., Coiffier, B.[2021]

Brentuximab vedotin (BV) combined with cyclophosphamide, doxorubicin, and prednisone (BV-CHP) has shown improved outcomes in treating common nodal CD30+ peripheral T-cell lymphomas (PTCLs) compared to the traditional treatment regimen, indicating a significant advancement in therapy.

Further research is needed to determine the optimal level of CD30 expression for effective BV-CHP therapy and to assess its efficacy and safety in less common subtypes of CD30+ PTCLs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of CD30+ PTCL. Barta, SK., Gong, JZ., Porcu, P.[2021]

In a study of 67 patients with cutaneous T-cell lymphoma (CTCL), brentuximab vedotin (BV) demonstrated a 67% overall response rate, with particularly high efficacy in patients with CD30+ lymphoproliferative disorders (84%) and folliculotropic mycosis fungoides (71%).

The treatment was generally well-tolerated, with the most common side effect being peripheral neuropathy, which was mostly mild (grades 1 or 2) in 57% of patients, indicating that BV is both effective and relatively safe for advanced-stage CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry. Muniesa, C., Gallardo, F., García-Doval, I., 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 significantly reduced symptom burden in patients with CD30-expressing cutaneous T-cell lymphoma compared to physician's choice treatments, with a mean maximum reduction in symptom scores of -27.96 versus -8.62, exceeding the minimally important difference.

Quality of life measures, including FACT-G and EQ-5D scores, remained comparable between brentuximab vedotin and physician's choice, indicating that the treatment did not adversely affect patients' overall well-being, even in those experiencing peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Dummer, R., Prince, HM., Whittaker, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12539070/

PMC - PubMed Central BV‐CHP demonstrated high ORR and CRR across age groups and ATL subtypes with a manageable safety profile, supporting its potential use as a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03113500

Study Details | NCT03113500 | Brentuximab Vedotin and ... Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma. Detailed Description.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1692/499263/Final-Results-of-a-Multicenter-Pilot-Study

Final Results of a Multicenter Pilot Study Evaluating ... Brentuximab vedotin (BV) is a CD30 targeting antibody-drug conjugate that is effective in treating many types of lymphoma, including CD30+ ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123082952

Final Results of a Multicenter Pilot Study Evaluating ... In this final analysis, BV-CHEP was safe and effective for the treatment of aggressive ATLL. High ORR and CR rates were achieved regardless of CD30 status.

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

Brentuximab Vedotin (SGN-35) for Relapsed CD30- ... Of the 45 patients who were treated, 42 had Hodgkin's lymphoma, 2 had systemic ALCL, and 1 had CD30-positive angioimmunoblastic T-cell lymphoma ...

6. adcetrispro.com adcetrispro.com/classical-hodgkin-lymphoma-post-auto-hsct-consolidation/safety

ADCETRIS® (brentuximab vedotin) Safety Info The most common serious adverse reactions were pneumonia (4%), pyrexia (4%), vomiting (3%), nausea (2%), hepatotoxicity (2%), and peripheral sensory neuropathy ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/adcetris-epar-product-information_en.pdf

Adcetris, INN-brentuximab vedotin - EMA ADCETRIS is indicated for the treatment of adult patients with CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant ( ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/125388Orig1s108lbl.pdf

highlights of prescribing information - accessdata.fda.gov Data summarizing ADCETRIS exposure are also provided for 347 patients with T-cell lymphoma, including 223 patients with PTCL who received ADCETRIS in ...

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

Brentuximab vedotin - PMC Several trials have shown durable antitumor activity with a manageable safety profile in patients with relapsed/refractory Hodgkin lymphoma, systemic anaplastic ...