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

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

16 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Brentuximab Vedotin for treating Adult T-Cell Leukemia/Lymphoma?

Brentuximab Vedotin has shown promise in treating adult T-cell leukemia/lymphoma, especially in patients with CD30-positive tumors, as it has been effective in similar conditions like peripheral T-cell lymphoma. In one case, a patient with aggressive adult T-cell leukemia/lymphoma achieved remission with Brentuximab Vedotin combined with chemotherapy and maintained it with ongoing treatment. ^{1 2 3 4 5}

Is Brentuximab Vedotin safe for humans?

Brentuximab Vedotin has been shown to be generally safe in humans, including older adults, with some patients experiencing serious side effects. In studies, it was used to treat various types of lymphomas, and while it can cause significant side effects, dose adjustments can help manage these issues. ^{1 6 7 8 9}

How is the drug Brentuximab Vedotin + CHEP different from other treatments for adult T-cell leukemia/lymphoma?

Brentuximab Vedotin + CHEP is unique because it targets CD30, a protein often found on the surface of adult T-cell leukemia/lymphoma cells, and combines this targeted approach with chemotherapy. This combination has shown promise in improving outcomes for patients with CD30-positive lymphomas, especially those who are not eligible for stem cell transplantation. ^{1 2 5 8 10}

What is the purpose of this trial?

Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in the United States occur along the East Coast due to emigration from the Caribbean islands. There is currently no standard treatment for ATLL. Research shows that patients who go into first time remission (respond completely or partially to treatment) and have a bone marrow transplant have the best outcomes. Traditional chemotherapy treatments have generally not worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone marrow transplant. The purpose of this study is to see how well individuals with ATLL respond to an investigational cancer treatment. This investigational treatment combines a drug called brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide, doxorubicin, etoposide, and prednisone. This treatment is considered investigational because it is not approved by the United States Food and Drug Administration (FDA) for the treatment of ATLL. Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose cancer cells express a type of marker called CD30. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of the immune system. They can stick to and attack specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target called cluster of differentiation 30 (CD30) that is located on the outside of the cancer cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a larger amount of CD30 on their surface than normal cells. However, CD30 is found in different amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each participant's cancer cells. Researchers will be looking to see if the response to the study treatment varies based on the amount of CD30 found on the outside participants' cancer cells. In another study, brentuximab vedotin was combined in another study with cyclophosphamide, doxorubicin, and prednisone. The study included patients with various types of T-cell lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone. They predict that the addition of etoposide will improve patient outcomes. Research shows that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.

Research Team

Dittus Christopher, DO, MPH

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

References

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

Successful treatment with brentuximab vedotin for relapsed and refractory adult T cell leukemia. [2021]

2. 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]

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

Time has come for immunotherapy in PTCL. [2021]

4. 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]

5. Japan pubmed.ncbi.nlm.nih.gov

Successful Treatment of an Aggressive Adult T-cell Leukemia/Lymphoma with Strong CD30 Expression Using Brentuximab Vedotin as Combination and Maintenance Therapy. [2023]

6. England 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. [2020]

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

Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry. [2022]

9. United States 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. [2019]

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

Brentuximab vedotin in the treatment of CD30+ PTCL. [2021]