Chemotherapy + Radiotherapy for Hodgkin's Lymphoma

Recruiting at 7 trial locations

Overseen By Matthew J. Ehrhardt

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: CD30 negative HL, Prior therapy, Inadequate organ function, 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

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

Trial Summary

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 trial coordinators or your doctor.

What data supports the effectiveness of the chemotherapy and radiotherapy treatment for Hodgkin's Lymphoma?

Research shows that the BEABOVP regimen, which includes bendamustine, is being used as a frontline treatment for pediatric Hodgkin lymphoma with promising results. Additionally, the T(R)EC regimen, which includes bendamustine, demonstrated high response rates in patients with relapsed or refractory Hodgkin lymphoma, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiotherapy generally safe for treating Hodgkin's Lymphoma?

The safety of chemotherapy drugs like doxorubicin, bleomycin, vinblastine, and dacarbazine, used in Hodgkin's Lymphoma treatment, has been studied, showing that they are generally well-tolerated with mild and temporary side effects. However, nausea and vomiting are common side effects, and antiemetic (anti-nausea) medications are often used to manage these symptoms effectively. ^{6 7 8 9 10}

What makes the chemotherapy and radiotherapy treatment for Hodgkin's Lymphoma unique?

This treatment combines multiple drugs, including Bendamustine, Brentuximab Vedotin, and others, which are not typically used together in standard regimens like ABVD or Stanford V. The inclusion of these drugs may offer a novel approach by potentially enhancing effectiveness or reducing toxicity compared to traditional treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

This is a phase II study using risk and response-adapted therapy for low, intermediate and high risk classical Hodgkin lymphoma. Chemotherapy regimens will be based on risk group assignment. Low-risk and intermediate- risk patients will be treated with bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine, and prednisone (BEABOVP) chemotherapy. High-risk patients will receive Adcetris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) (AEPA) and cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC) (CAPDac) chemotherapy. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an adequate response (AR) after 2 cycles of therapy for all risk groups.

Research Team

Matthew J. Ehrhardt

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults up to age 25 with untreated CD30+ classical Hodgkin lymphoma. Eligible participants have various stages of the disease, adequate organ function, and no prior therapy for Hodgkin's except limited emergency treatments. They must be able to perform normal activities without significant breathing issues.

Inclusion Criteria

My cancer is in an early stage without significant spread.

I was diagnosed before my 22nd birthday.

I agree to use effective birth control during the study.

Exclusion Criteria

CD30 negative HL

I have a severe nerve condition that affects my ability to assess nerve damage.

I am unable or unwilling to give my consent for participation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Low-risk and intermediate-risk patients receive BEABOVP chemotherapy; high-risk patients receive AEPA and CAPDac chemotherapy

8 months

Radiotherapy

Residual node radiotherapy is given at the end of all chemotherapy to involved nodes that do not have an adequate response after 2 cycles of therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Bendamustine
• Bleomycin
• Brentuximab Vedotin
• Cyclophosphamide
• Doxorubicin
• DTIC
• Etoposide
• Filgrastim
• Prednisone
• Radiotherapy
• Vinblastine
• Vincristine

Trial Overview The study tests different chemotherapy combinations based on risk levels: low/intermediate-risk patients receive BEABOVP regimen; high-risk patients get AEPA and CAPDac regimens. Some may also need radiotherapy if their nodes don't respond well after two cycles of chemo.

Participant Groups

Group I: Low-Risk Experimental Treatment 10 Interventions

Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

Group II: Intermediate-Risk Experimental Treatment 10 Interventions

Participants receive 3 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

Group III: High-Risk Experimental Treatment 9 Interventions

Participants receive 2 cycles of AEPA: Adcedris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) and 4 cycles of CAPDac: cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC). For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

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

Teva Pharmaceuticals USA

Industry Sponsor

Trials

232

Recruited

189,000+

Dr. Eric A. Hughes

Teva Pharmaceuticals USA

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Pharmaceuticals USA

Chief Executive Officer since 2023

BSc in Biochemistry from Imperial College London

Findings from Research

In a study involving 20 pediatric patients with low- and intermediate-risk Hodgkin lymphoma, a single-day dose of 180 mg/m2 of bendamustine was found to be safe and well tolerated, with no significant toxicities causing treatment delays.

Age was a factor influencing the clearance of bendamustine, accounting for 23% of variability among individuals, but this did not impact the overall safety and tolerability of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of bendamustine in the BEABOVP regimen for the treatment of pediatric patients with Hodgkin lymphoma. Purvis, KN., Swanson, HD., Niloy, KK., et al.[2023]

The T(R)EC regimen, which replaces ifosfamide with bendamustine, demonstrated high response rates of 85% in classic Hodgkin lymphoma and 65% in diffuse large B cell lymphoma, indicating its efficacy as a treatment for relapsed or refractory cases.

This outpatient treatment was found to be safe, with no dose-limiting toxicities and successful stem cell collection in 30 out of 32 patients, making it a promising alternative to the traditional (R)ICE regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. Budde, LE., Wu, D., Martin, DB., et al.[2022]

The chemotherapy regimen combining MOPP/EBV/CAD resulted in a high response rate, with 93% of 80 patients achieving complete or partial remission for advanced Hodgkin's disease, demonstrating its efficacy.

While the treatment showed promising results, it also led to significant hematologic toxicity, including one fatal case of gastrointestinal bleeding, highlighting the need for caution in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group. Gobbi, PG., Pieresca, C., Federico, M., et al.[2017]

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 involving 181 patients with unfavorable stage IA and IIA Hodgkin's lymphoma, both the ABVD and EVE chemotherapy regimens achieved similar complete remission rates (93% for ABVD and 92% for EVE).

However, the ABVD regimen demonstrated significantly better 5-year relapse-free survival (95% for ABVD vs. 78% for EVE) and failure-free survival (90% for ABVD vs. 73% for EVE), indicating that EVE is not recommended as an initial treatment for Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study. Pavone, V., Ricardi, U., Luminari, S., et al.[2020]

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 61 patients with non-Hodgkin lymphoma undergoing bendamustine-based chemotherapy, both granisetron and palonosetron effectively controlled chemotherapy-induced nausea and vomiting (CINV), with complete control achieved in all patients during the acute phase.

Granisetron monotherapy was found to be as effective and safe as palonosetron combination therapy for preventing delayed CINV, suggesting that granisetron alone could be a cost-effective option for managing CINV in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. Uchida, M., Nakamura, T., Makihara, Y., et al.[2019]

In a study of 60 patients with Hodgkin's disease undergoing a polychemotherapy regimen, 97% experienced nausea and 91% severe vomiting, leading to significant distress and a 26.6% rate of patient noncompliance.

High-dose metoclopramide, either alone or combined with high-dose methylprednisolone, was found to be extremely effective in controlling chemotherapy-induced vomiting, outperforming haloperidol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of vomiting induced by polychemotherapy in Hodgkin's disease]. Berényi, E., Kiss, E.[2013]

A study analyzing data from 45,324 chemotherapy-treated patients across five European countries found that only 15% of patients receiving highly emetogenic chemotherapy (HEC) or carboplatin were given the recommended antiemetic combination of NK1 receptor antagonist, 5-HT3 receptor antagonist, and dexamethasone.

Additionally, 12% of patients received no antiemetic treatment at all, highlighting a significant gap in adherence to established antiemetic guidelines, which could lead to increased nausea and vomiting during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data. Aapro, M., Scotté, F., Escobar, Y., et al.[2021]

In a retrospective study of various highly emetogenic chemotherapy regimens, complete control of nausea and vomiting was achieved in over 70% of patients with the GEM/CDDP and R-CHOP21 regimens, indicating effective antiemetic management for these specific treatments.

The addition of aprepitant (APR) significantly improved complete response rates in patients receiving the 5-FU/CDDP regimen, but not in those on EPI/CPA, highlighting the need for tailored antiemetic strategies based on the specific chemotherapy regimen's emetogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant. Aoki, S., Iihara, H., Nishigaki, M., et al.[2021]

In a pilot study of 26 patients with advanced Hodgkin's disease, the combination chemotherapy regimen of etoposide, vinblastine, and doxorubicin (EVA) resulted in a 54% complete response rate, but also showed a significant induction failure rate of 46%.

The study indicated that the EVA regimen may not be more effective than existing treatments and raises concerns about potential long-term toxicity, particularly leukemogenic risks associated with etoposide, suggesting a need for new treatment combinations without this agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease. Brizel, DM., Gockerman, JP., Crawford, J., et al.[2019]

In a study of 399 patients with limited-stage Hodgkin's lymphoma, those receiving radiation therapy in addition to ABVD chemotherapy had a higher 5-year freedom from disease progression (93%) compared to those receiving ABVD alone (87%).

Despite the improved disease progression outcomes with radiation therapy, there was no significant difference in overall survival between the two treatment groups, indicating that while radiation may help prevent disease recurrence, it does not necessarily extend life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. Meyer, RM., Gospodarowicz, MK., Connors, JM., et al.[2013]

In a study of 30 patients with early-stage Hodgkin's disease, the combination of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy followed by involved-field radiotherapy resulted in a high response rate, with 27 patients achieving complete remission after treatment.

Despite its effectiveness, the VBM regimen was associated with significant toxicity, including pulmonary issues and neutropenic sepsis, which raises concerns about its routine use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study. Bates, NP., Williams, MV., Bessell, EM., et al.[2017]

The British National Lymphoma Investigation (BNLI) has shown that MOPP chemotherapy is more effective than MOP, and that LOPP is equally effective as MOPP but with less acute toxicity, highlighting the importance of optimizing chemotherapy regimens for Hodgkin's disease.

High-dose BEAM chemotherapy followed by autologous bone marrow transplantation is superior for treating poor-risk relapsed and refractory Hodgkin's disease, indicating a promising approach for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation. Zekri, JM., Mouncey, P., Hancock, BW.[2019]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of bendamustine in the BEABOVP regimen for the treatment of pediatric patients with Hodgkin lymphoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. [2022]

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

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group. [2017]

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

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

5. England pubmed.ncbi.nlm.nih.gov

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study. [2020]

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. Germany pubmed.ncbi.nlm.nih.gov

Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. [2019]

8. Hungary pubmed.ncbi.nlm.nih.gov

[Management of vomiting induced by polychemotherapy in Hodgkin's disease]. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant. [2021]

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

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease. [2019]

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

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. [2013]

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

Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study. [2017]

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

Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation. [2019]

15. 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]