Chemotherapy + Radiation for Hodgkin's Lymphoma

Recruiting at 5 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Intermediate/high risk 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

Compensation: Varies

Number of Visits: Unknown

88 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 treatment combining chemotherapy and radiation for Hodgkin's Lymphoma?

Research shows that the Stanford V regimen, which includes drugs like doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone, combined with radiation therapy, is safe and effective for treating Hodgkin's Lymphoma. Additionally, the ABVD regimen, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, is a standard treatment for advanced Hodgkin's Lymphoma and has been shown to be effective. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation therapy safe for treating Hodgkin's Lymphoma?

The combination of chemotherapy drugs like doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with radiation therapy has been studied for safety. In older patients, there is a risk of lung toxicity from bleomycin, especially with more than two cycles of treatment, which can be severe and sometimes fatal. Overall, the safety profile varies, and older patients may experience higher toxicity rates. ^{1 3 5 6 7}

How does the Stanford V regimen differ from other treatments for Hodgkin's Lymphoma?

The Stanford V regimen is unique because it combines multiple chemotherapy drugs with radiation therapy, aiming to maximize effectiveness while minimizing treatment duration. It includes a specific combination of drugs like mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone, which is different from the more commonly used ABVD regimen. ^{2 3 8 9 10}

What is the purpose of this trial?

This phase II trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with favorable-risk Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, mechlorethamine hydrochloride, vincristine sulfate, bleomycin, etoposide, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells for those patients that still had residual cancer at the end of chemotherapy. Giving combination chemotherapy with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started.

Research Team

Matt Ehrhardt, MD, MS

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for young patients, 21 years or younger, with a type of cancer called favorable-risk Hodgkin lymphoma. They should not have been treated before and must have specific early stages of the disease without extensive spread. Girls after puberty need a negative pregnancy test and all participants able to have children must use birth control.

Inclusion Criteria

My cancer is early stage with limited spread and no extranodal involvement.

Female patients who are post-menarchal must have a negative pregnancy test. Patients of reproductive potential must agree to use an effective contraceptive method

If my disease is reassessed as intermediate risk, I will be taken off the HOD08 trial.

Exclusion Criteria

My cancer is at an advanced stage or has specific high-risk features.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive Stanford V chemotherapy regimen over 8 weeks

8 weeks

Weekly visits for IV administration

Radiation

Patients not achieving complete response undergo radiation therapy to individual nodal sites

2-3 weeks after chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

median 2 years post therapy

Treatment Details

Interventions

• Bleomycin
• Doxorubicin Hydrochloride
• Etoposide
• Mechlorethamine Hydrochloride
• Prednisone
• Radiation Therapy
• Vinblastine
• Vincristine Sulfate

Trial Overview The study is testing how well a mix of chemotherapy drugs works compared to the same chemo plus radiation therapy in these young patients. The goal is to see if adding radiation helps more when some cancer remains after chemo, while trying to preserve healthy body parts.

Participant Groups

Group I: Treatment Experimental Treatment 2 Interventions

Participants receive Stanford V Chemotherapy with or without radiation therapy. Patients receive doxorubicin hydrochloride IV and vinblastine IV on day 1 of weeks 1, 3, 5, and 7; mechlorethamine hydrochloride IV on day 1 of weeks 1 and 5; vincristine sulfate IV and bleomycin IV on day 1 of weeks 2, 4, 6, and 8; etoposide IV on day 1 of weeks 3 and 7; and prednisone orally (PO) three times daily every other day of weeks 1-8. Beginning 2-3 weeks after completion of chemotherapy, patients not achieving complete response undergo radiation therapy to individual nodal sites (tailored fields)

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

Approved in European Union as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Approved in United States as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Approved in Canada as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

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]

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]

References

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

ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. [2015]

2. 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]

3. 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]

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

ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. [2022]

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

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

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

The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. [2021]

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

Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. [2021]

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

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group. [2017]

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

Twenty-year disease and treatment-associated mortality rates of patients with Hodgkin lymphoma of clinical stages IIIB and IV prospectively treated with 3-month anthracycline-based chemotherapy followed by extended high-dose radiation. [2013]

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

MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial. [2017]