Chemotherapy + Radiotherapy for Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Matthew J. Ehrhardt

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: St. Jude Children's Research Hospital

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

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}

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.

Trial 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 (Alkylating agents)
• Bleomycin (Antineoplastic Agent)
• Brentuximab Vedotin (Monoclonal Antibodies)
• Cyclophosphamide (Alkylating agents)
• Doxorubicin (Anti-tumor antibiotic)
• DTIC (Alkylating agents)
• Etoposide (Topoisomerase II inhibitors)
• Filgrastim (Growth Factor)
• Prednisone (Corticosteroid)
• Radiotherapy (Radiation)
• Vinblastine (Vinca alkaloids)
• Vincristine (Vinca alkaloids)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Lucile Packard Children's Hospital Stanford University Palo Alto, CA

St. Jude Affiliate Baton Rouge Clinic (Our Lady of the Lakes Regional Medical Center) Baton Rouge, LA

St. Jude Children's Research Hospital Memphis, TN

St. Jude Midwest Affiliate - Peoria Peoria, IL

More Trial Locations

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital Lead Sponsor

Seagen Inc. Industry Sponsor

Teva Pharmaceuticals USA Industry Sponsor

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] Label="PURPOSE">The Stanford V chemotherapy regimen has been used to treat Hodgkin lymphoma (HL) patients since 2002 with excellent cure rates; however, mechlorethamine is no longer available. Bendamustine, a drug structurally similar to alkylating agents and nitrogen mustard, is being substituted for mechlorethamine in combination therapy in a frontline trial for low- and intermediate-risk pediatric HL patients, forming a new backbone of BEABOVP (bendamustine, etoposide, doxorubicin, bleomycin, vincristine, vinblastine, and prednisone). This study evaluated the pharmacokinetics and tolerability of a 180&#160;mg/m2 dose of bendamustine every 28&#160;days to determine factors that may explain this variability.

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] We sought to develop a safe and effective outpatient salvage regimen by replacing ifosfamide within the (R)ICE (rituximab, ifosfomide, carboplatin, etoposide) regimen with bendamustine (T(R)EC) via a multicentre phase I/II study for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). Therapy consisted of 60-120&#160;mg/m2 per day bendamustine on days 1 and 2 in combination with carboplatin, etoposide and rituximab (only for CD20+ lymphoma) used in the (R)ICE regimen for up to 2 cycles. The objectives were to define a maximally tolerated dose (MTD) of bendamustine, determine safety and toxicity, assess efficacy, and evaluate impact on stem cell collection. Forty-eight patients were treated of which 71% had refractory disease. No dose-limiting toxicities were observed. The recommended phase II dose of bendamustine was 120&#160;mg/m2 per day on days 1 and 2. Response rates were 85% (70% complete response, CR) in HL, and 65% (40% CR) in DLBCL. Stem cell collection was successful in 30 of 32 patients. The most common non-haematological toxicities &#8805;grade 3 were febrile neutropenia (8%) and dehydration (8%). The T(R)EC regimen safely yields high response rates, successfully mobilizes peripheral blood stem cells and compares favourably to RICE, offering an effective outpatient treatment option for patients with relapsed or refractory DLBCL and HL.

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] We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD).

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

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. [2021] To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).

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] In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program.

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] We analyzed safety of NEPA (netupitant/palonosetron) and dexamethasone (NEPA+DEX) for the management of chemotherapy-induced nausea and vomiting (CINV) in classical Hodgkin's lymphoma patients that experienced CINV with a prophylaxis with palonosetron (PALO + DEX). In a retrospective, monocentric, noncomparative study, we analyzed adverse events and CINV grading in patients who switched from PALO + DEX to NEPA + DEX. Among 32 patients treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) during the study period, 47% did not properly control CINV with PALO + DEX and were shifted to NEPA + DEX. Among these, 53.3% properly controlled CINV is for all the remaining chemotherapy cycles. We did not observe an increase of adverse events after switching to NEPA. In our study, NEPA did not show drug-drug interaction with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy agents and NEPA administration was well tolerated with mild and transient adverse events.

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

Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. [2019] The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.

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

[Management of vomiting induced by polychemotherapy in Hodgkin's disease]. [2013] Sixty patients with Hodgkin's disease were treated with a polychemotherapy regimen including very emetic dacarbazine and adriamycin in addition to bleomycin and vincristine on 622 treatment days during the last 10 years. Nausea in 97% and severe vomiting in 91% were observed during the treatment causing considerable distress to patients which led to patient noncompliance in 26.6%. Among the used antiemetic agents haloperidol was less active than high-dose metoclopramide alone or with high-dose methylprednisolone which were extremely effective. The control and prevention of drug-induced emesis is a major problem for cancer patients and their oncologists. The present situation and the home tasks are also discussed on the basis of literature and their observations.

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] Label="BACKGROUND">Guideline-recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide (AC)- and carboplatin (considered moderately emetogenic chemotherapy)-based chemotherapy. Here, we analyze the use of NK1 RA-5-HT3 RA-dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin.

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

Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant. [2021] Although antiemetic medication based on the emetogenicity of the cancer chemotherapy regimen is recommended, emetic control varies even among highly emetogenic chemotherapy (HEC). In the present study, we retrospectively investigated the rates of emetic control by a combination of granisetron, 5-HT3 antagonist and dexamethasone in various HEC regimens, including 5 single-day chemotherapy regimens such as gemcitabine/cisplatin (GEM/CDDP), epirubicin/cyclophosphamide (EPI/CPA), pemetrexed or vinorelbine/cisplatin (PEM or VNR/CDDP), doxorubicin/bleomycin/vinblastine/dacarbazine (ABVd) and rituximab/doxorubicin/cyclophosphamide/vincristine/prendisolone (R-CHOP21), and 2 multiple-day chemotherapy regimens such as 5-fluorouracil/cisplatin (5-FU/CDDP) and bleomycin/etoposide/cisplatin (BEP). Complete response (no emesis, no rescue treatment) during the overall period (days 1-5) was assessed as the primary endpoint. Chemotherapy-induced nausea and vomiting was well-controlled (complete response &gt;70%) in GEM/CDDP and R-CHOP21, but not in other regimens. The effect of a triple antiemetic medication including aprepitant (APR) was subsequently examined in patients receiving EPI/CPA and 5-FU/CDDP. Complete response was significantly improved in patients receiving 5-FU/CDDP but not in those receiving EPI/CPA, although the complete protection from vomiting significantly increased in both cases. Of note, the administration of APR for 5 days, but not for 3 days, was required to completely block the incidence of vomiting during the 7 days of the observation period in patients receiving 5-FU/CDDP. These findings suggest that APR should be used appropriately based on the emetogenicity of HEC regimens.

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] Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD.

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] We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma.

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] To assess the efficacy and toxicity of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease.

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] Hodgkin's disease demonstrates an exquisite sensitivity to chemotherapy and radiation therapy. This necessitates investigation of modes of delivering these modalities in the best possible fashion to improve outcomes. The British National Lymphoma Investigation (BNLI) has conducted randomized trials in advanced Hodgkin's disease for > 30 years. The results of BNLI studies have demonstrated that MOPP (mechlorethamine/vincristine/procarbazine/prednisone) chemotherapy is superior to MOP (mechlorethamine/vincristine/procarbazine) chemotherapy; that there are no significant differences between MOPP and B-MOPP (MOPP plus bleomycin); that there is no significant benefit from maintenance therapy with lomustine/vinblastine/bleomycin; that LOPP (chlorambucil/vincristine/procarbazine/prednisone) is as effective as MOPP and has less acute toxicity; that alternating therapy with LOPP and EVAP (etoposide/vinblastine/doxorubicin/prednisolone) is superior to EVAP alone or hybrid LOPP and EVA (etoposide/vinblastine/doxorubicin); that alternating therapy with ChlVPP (a substitute for MOPP) and prednisolone/doxorubicin/bleomycin/vincristine/etoposide regimens is superior to the latter regimen alone; that the Stanford V regimen (doxorubicin/vinblastine/mechlorethamine/vincristine/bleomycin/etoposide/prednisone) combined with disciplined radiation therapy is safe and effective; that hybrid therapy with ChlVPP and EVA and alternating therapy with ChlVPP and prednisolone/doxorubicin/bleomycin/vincristine/etoposide are as effective as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) alone; and that there is no additional benefit from total nodal irradiation or combined-modality therapy compared with MOPP; and that treatment with high-dose BEAM (carmustine/etoposide/cytarabine/melphalan) and autologous bone marrow transplantation is superior to mini-BEAM (lower-dose BEAM not requiring bone marrow rescue) for poor-risk relapsed and refractory disease.

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] The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL).