Chemotherapy + Immunotherapy for Hodgkin's Lymphoma

Recruiting at 9 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, CNS involvement, Hepatic insufficiency, 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: 22

82 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or medications that could interfere with the trial, you may need to stop them. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination including Brentuximab Vedotin, Doxorubicin, Vinblastine, and Dacarbazine for treating Hodgkin's Lymphoma?

Research shows that the combination of Brentuximab Vedotin with Doxorubicin, Vinblastine, and Dacarbazine (A+AVD) provides long-term benefits in progression-free survival for patients with advanced Hodgkin's Lymphoma, compared to the traditional ABVD regimen. This combination has shown potential benefits in overall survival, especially in patients with stage III or IV Hodgkin's Lymphoma. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs like doxorubicin, vinblastine, and dacarbazine safe for humans?

The combination of chemotherapy drugs doxorubicin, vinblastine, and dacarbazine was generally well tolerated in patients, with mild and temporary side effects. No increase in adverse events was observed when these drugs were used with NEPA, a medication to manage nausea and vomiting. ^{6 7 8 9 10}

What makes the chemotherapy and immunotherapy drug combination unique for treating Hodgkin's Lymphoma?

This treatment combines chemotherapy drugs like doxorubicin and dacarbazine with immunotherapy drugs like nivolumab, which helps the immune system target cancer cells more effectively. Brentuximab vedotin, a key component, specifically targets CD30-positive cancer cells, which are common in Hodgkin's Lymphoma, making it a targeted approach compared to traditional chemotherapy regimens. ^{1 3 5 11 12}

What is the purpose of this trial?

This phase II trial evaluates how well AVD (doxorubicin, vinblastine, dacarbazine) in combination with brentuximab vedotin and nivolumab work in treating patients with stage I-II Hodgkin lymphoma. Drugs used in the chemotherapy, such as doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, and/or by stopping them from spreading. Targeted agent, such as nivolumab, may interfere with the ability of cancer cells to grow and spread by enhancing the immune system. Giving doxorubicin, vinblastine, dacarbazine, brentuximab vedotin, and nivolumab may improve survival of patients with stage I-II Hodgkin lymphoma.

Research Team

Steven I Park

Principal Investigator

Academic and Community Cancer Research United

Eligibility Criteria

This trial is for adults with previously untreated stage I-II non-bulky Hodgkin lymphoma. Participants must have measurable disease, adequate blood counts and organ function, no severe infections or other health conditions that could interfere with the study, not be pregnant or nursing, and agree to use contraception. Those with certain prior treatments, immunodeficiency, active hepatitis B or C, another primary malignancy within 3 years (with some exceptions), uncontrolled illnesses or known allergies to study drugs are excluded.

Inclusion Criteria

My hemoglobin level is at least 8.5 g/dL without recent blood transfusions.

My white blood cell count is healthy without needing a recent blood transfusion.

My cancer can be measured and is at least 1.5 cm big on a CT scan.

Exclusion Criteria

I have a large tumor (10 cm or larger) according to a CT scan.

I am not taking any experimental drugs for my cancer.

I have not had severe infections, pancreatitis, stroke, or TIA in the recent past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin every 28 days for 3 cycles

12 weeks

6 visits (in-person)

Consolidation Therapy

PET-positive participants receive brentuximab vedotin and nivolumab every 2 weeks for 4 cycles, followed by nivolumab alone for 8 cycles; PET-negative participants receive nivolumab every 2 weeks for 8 cycles

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 4 and 8 weeks, every 3 or 6 months for 2 years, then annually for 3 years

Treatment Details

Interventions

• Brentuximab Vedotin
• Dacarbazine
• Doxorubicin
• Nivolumab
• Vinblastine

Trial Overview The trial tests a combination of chemotherapy drugs (doxorubicin, vinblastine, dacarbazine) alongside brentuximab vedotin and nivolumab in patients with early-stage Hodgkin lymphoma. The aim is to see if this regimen can improve survival by killing cancer cells directly while also boosting the immune system's ability to fight cancer.

Participant Groups

Group I: Treatment (combination chemotherapy, nivolumab) Experimental Treatment 6 Interventions

Patients receive doxorubicin IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine IV over \>= 30 minutes, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET-positive then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. PET-positive patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. PET-negative patients receive nivolumab IV over 30 minutes on day 1 starting after AVD and BV treatment. Treatment repeats every 2 weeks for 8 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?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 170 patients with early-stage unfavorable Hodgkin lymphoma, the combination of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) resulted in a higher PET-negative response rate (82.3%) after two cycles compared to the standard ABVD treatment (75.4%).

The 2-year progression-free survival (PFS) rate was also higher in the BV-AVD group (97.3%) compared to the ABVD group (92.6%), indicating that BV-AVD may offer a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. Fornecker, LM., Lazarovici, J., Aurer, I., et al.[2023]

In the phase III ECHELON-1 study involving 1,334 patients, older patients (aged ≥60) with classical Hodgkin lymphoma showed similar modified progression-free survival rates at 24 months when treated with brentuximab vedotin plus AVD (70.3%) compared to ABVD (71.4%).

While A+AVD demonstrated comparable efficacy to ABVD, it was associated with higher rates of grade 3/4 peripheral neuropathy (18% vs. 3%) and febrile neutropenia (37% vs. 17%), but lower rates of pulmonary toxicity, with no pulmonary-related deaths in the A+AVD group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Evens, AM., Connors, JM., Younes, A., et al.[2022]

A systematic review of 62 randomized controlled trials found that the five-year overall survival rates for ABVD and BEACOPP regimens in advanced-stage Hodgkin lymphoma were 60-97% and 84-99%, respectively, indicating high efficacy for both treatments.

The new treatment A+AVD showed improved efficacy compared to ABVD while maintaining an acceptable tolerability profile, suggesting it may be a more manageable option for patients with advanced-stage Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. Dalal, M., Gupta, J., Price, K., et al.[2021]

In a study of 1334 patients with untreated stage III or IV Hodgkin's lymphoma, those treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) showed a significant overall survival advantage compared to those receiving the standard ABVD regimen, with a 6-year survival rate of 93.9% versus 89.4%.

A+AVD also resulted in longer progression-free survival and fewer patients requiring subsequent therapies, although it was associated with a higher incidence of peripheral neuropathy, which mostly resolved by the last follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. Ansell, SM., Radford, J., Connors, JM., et al.[2022]

In a study of 32 classical Hodgkin's lymphoma patients, 47% experienced inadequate control of chemotherapy-induced nausea and vomiting (CINV) with palonosetron and dexamethasone, leading to a switch to netupitant and dexamethasone, which resulted in 53.3% achieving proper CINV control for subsequent cycles.

The switch to NEPA (netupitant/palonosetron) did not increase adverse events compared to the previous treatment, indicating that NEPA is well tolerated and does not interact negatively with standard chemotherapy agents like ABVD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of netupitant/palonosetron and dexamethasone in classical Hodgkin's lymphoma patients with inadequate chemotherapy-induced nausea and vomiting prophylaxis with palonosetron and dexamethasone: a single-center real-life experience. Zilioli, VR., Muzi, C., Minga, P., et al.[2020]

In a study of 88 patients with non-Hodgkin lymphoma receiving moderately emetogenic chemotherapy, palonosetron demonstrated increasing efficacy, with complete response rates rising from 68.2% in the first cycle to 80.5% in the second cycle, and over 90% of patients remained emesis-free without additional antiemetics.

Palonosetron showed a favorable safety profile, with only 8% of treatment-emergent adverse events related to the drug, indicating it is a safe option for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase IV study of palonosetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with non-Hodgkin lymphomas undergoing repeated cycles of moderately emetogenic chemotherapy. Choi, BS., Borsaru, GP., Ballinari, G., et al.[2021]

In a phase III trial involving 794 patients, the study found that both ABVD and Stanford V chemotherapy regimens had similar efficacy in treating stage I or II bulky mediastinal Hodgkin lymphoma, with overall response rates of 83% and 88%, respectively.

At a median follow-up of 6.5 years, there were no significant differences in 5-year failure-free survival (85% for ABVD vs. 79% for Stanford V) or overall survival (96% for ABVD vs. 92% for Stanford V), indicating that both treatment options are viable for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. Advani, RH., Hong, F., Fisher, RI., et al.[2021]

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]

References

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

Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. [2022]

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

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. [2021]

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

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. [2022]

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

Safety and efficacy of single-agent bendamustine after failure of brentuximab vedotin in patients with relapsed or refractory hodgkin's lymphoma: experience with 27 patients. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of netupitant/palonosetron and dexamethasone in classical Hodgkin's lymphoma patients with inadequate chemotherapy-induced nausea and vomiting prophylaxis with palonosetron and dexamethasone: a single-center real-life experience. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

A prospective study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in malignant lymphoma patients following highly emetogenic chemotherapy. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of indisetron hydrochloride for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer]. [2016]

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

Multicenter phase IV study of palonosetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with non-Hodgkin lymphomas undergoing repeated cycles of moderately emetogenic chemotherapy. [2021]

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

Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. [2021]

12. 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]