Surgery, Radiation & Chemotherapy for Early-Stage Hodgkin's Lymphoma

Recruiting at 209 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: Systemic corticosteroids

Disqualifiers: B symptoms, Bulk 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: 22

188 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial is studying how well surgery and/or combination chemotherapy with or without radiation therapy or observation only work in treating young patients with newly diagnosed stage I or stage II lymphocyte predominant Hodgkin disease (LPHD). Surgery may be an effective treatment for LPHD. Drugs used in chemotherapy, such as doxorubicin, vincristine, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you must not have had prior chemotherapy or radiotherapy and must be more than 30 days since taking systemic corticosteroids.

Is the combination of surgery, radiation, and chemotherapy safe for treating Hodgkin's lymphoma?

The combination of cyclophosphamide, doxorubicin, vincristine, and prednisone, often used in chemotherapy for Hodgkin's lymphoma, has been generally found to have acceptable safety, with some side effects like doxorubicin-related heart issues, especially in older patients. Radiation therapy and surgery are also commonly used treatments, and while they have their own risks, they are generally considered safe when administered by experienced medical professionals. ^{1 2 3 4 5}

How is the drug combination of Cyclophosphamide, Doxorubicin Hydrochloride, Prednisone, and Vincristine Sulfate unique for treating early-stage Hodgkin's Lymphoma?

This drug combination is unique because it combines surgery, radiation, and chemotherapy, which is not the standard approach for early-stage Hodgkin's Lymphoma, where ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) is more commonly used. The inclusion of surgery and the specific combination of drugs may offer a different mechanism of action and treatment schedule compared to traditional regimens. ^{1 4 6 7 8}

What data supports the effectiveness of the treatment for early-stage Hodgkin's Lymphoma?

Research shows that combinations of drugs like doxorubicin, vincristine, and prednisone, which are part of the treatment plan, have been effective in treating Hodgkin's lymphoma in various studies. Additionally, radiation therapy has been shown to improve outcomes when combined with chemotherapy in treating Hodgkin's lymphoma. ^{4 6 7 9 10}

Who Is on the Research Team?

Burton E Appel

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with newly diagnosed stage I or II lymphocyte predominant Hodgkin disease (LPHD) without bulk disease. They must have normal liver and kidney function, not be pregnant or breastfeeding unless only observing, agree to use contraception if of reproductive potential, and have no prior chemotherapy or radiotherapy.

Inclusion Criteria

I have not had any radiotherapy before.

I have been newly diagnosed with LPHD and haven't received any treatment.

No greater than 1.4 mg/dL (for female patients >= 13 years of age)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients with stage IA disease undergo surgery for complete resection of lymph nodes

1 week

1 visit (in-person)

Observation

Patients with confirmed complete resection are observed for recurrence

6-7 weeks

1 visit (in-person)

Combination Chemotherapy

Patients receive doxorubicin, vincristine, prednisone, and cyclophosphamide

9 weeks

3 cycles, each 21 days apart

Involved-Field Radiotherapy (IFRT)

Patients undergo radiotherapy if not in complete response after chemotherapy

2.8 weeks

14 treatments, 5 days a week

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, every 6 months for 3 years, annually for 5 years, then every 5 years for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Conventional Surgery
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Prednisone
• Radiation Therapy
• Vincristine Sulfate

Trial Overview The study tests the effectiveness of surgery alone or combined with chemotherapy drugs like doxorubicin hydrochloride, prednisone, cyclophosphamide, vincristine sulfate and/or radiation therapy in treating LPHD. The goal is to determine which treatment kills more cancer cells.

How Is the Trial Designed?

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

COMBINATION CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 10-30 minutes and cyclophosphamide IV over 1 hour on day 1, vincristine IV over 1 minute on days 1 and 8, and prednisone PO or IV two or three times daily on days 1-7. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve CR after 3 courses of therapy proceed to follow-up. Patients who do not achieve a CR proceed to involved-field radiotherapy. IFRT: Beginning within 3 weeks after completion of combination chemotherapy, patients undergo IFRT once daily, 5 days a week for 2.8 weeks (14 treatments).

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The OEPA-COPDAC chemotherapy regimen, which replaces procarbazine with etoposide and dacarbazine, was found to be tolerable in terms of toxicity for boys with Hodgkin's lymphoma, with hematotoxicity being less pronounced compared to the traditional COPP regimen.

After a median follow-up of 58.6 months, the overall survival rate was 97.4% and the event-free survival rate was 89.0%, indicating that OEPA-COPDAC is as effective as the standard OPPA-COPP regimen for treating intermediate and advanced stages of classical Hodgkin's lymphoma in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. Mauz-Körholz, C., Hasenclever, D., Dörffel, W., et al.[2022]

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]

Etoposide is a key drug in treating malignant lymphomas and Hodgkin's disease, showing broad activity across various subtypes and demonstrating single-agent efficacy comparable to older treatments like alkylating agents and doxorubicin.

The drug works by inhibiting protein synthesis and topoisomerase II, allowing it to provide effective cytotoxicity without cross-resistance, and is integrated into multiple treatment protocols, enhancing the overall management of these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease. O'Reilly, SE., Klimo, P., Connors, JM.[2019]

The combination of biweekly THP-COP chemotherapy and radiotherapy resulted in a high 5-year overall survival rate of 89% and a cause-specific survival rate of 90% in 41 patients with early-stage non-Hodgkin's lymphoma.

Despite some patients experiencing grade 4 neutropenia (12%), the treatment was well-tolerated, with 93% of patients completing the chemotherapy as scheduled, indicating that this regimen is both feasible and effective for low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Nishioka, T., Tsuchiya, K., Nishioka, S., et al.[2015]

The CEOP chemotherapy regimen, which substitutes epirubicin for doxorubicin, demonstrated a high efficacy with a complete remission rate of 64.3% in 186 patients with intermediate- or high-grade non-Hodgkin lymphoma, particularly benefiting elderly patients.

Long-term follow-up showed that 79.8% of patients who achieved complete remission remained disease-free at a median of 86.9 months, indicating that CEOP is not only effective but also well-tolerated, with no deaths from cardiac toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Rossini, F., Terruzzi, E., Perego, D., et al.[2015]

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]

Citations

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

LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. [2017]

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

Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. [2022]

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

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]

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

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease. [2019]

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

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. [2015]

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

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. [2015]

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

Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856. [2019]

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

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

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

ACR Appropriateness Criteria® on Hodgkin's lymphoma-unfavorable clinical stage I and II. [2011]