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

Not currently recruiting at 216 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of various treatments for young patients with newly diagnosed, early-stage Hodgkin's lymphoma. Researchers study how surgery, chemotherapy (including drugs like Cyclophosphamide, Doxorubicin Hydrochloride, Prednisone, and Vincristine Sulfate), and radiation therapy, either alone or in combination, can stop cancer cell growth. The treatments aim to kill cancer cells or prevent them from dividing. This trial suits those newly diagnosed with stage I or stage II lymphocyte predominant Hodgkin disease without severe symptoms or large tumors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to significant advancements in cancer treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the chemotherapy drugs used in this trial for early-stage Hodgkin's lymphoma are generally safe. Doxorubicin hydrochloride, one of these drugs, is effective but can have side effects. For instance, it might cause heart problems if given in high doses, so doctors carefully monitor the total amount administered.

Cyclophosphamide, another drug in the trial, treats various cancers, including Hodgkin's lymphoma. It can cause side effects like nausea or hair loss, and in rare cases, it might lead to bladder issues or affect fertility.

Vincristine sulfate is also part of the treatment. It is usually well-tolerated but can sometimes cause nerve problems, leading to tingling or numbness in the fingers and toes.

Lastly, prednisone, a steroid, helps reduce swelling and supports chemotherapy. It can cause side effects like increased hunger, mood swings, or difficulty sleeping.

Overall, these drugs are commonly used, and doctors know how to manage their side effects. This trial is in an early phase, gathering information to confirm the safety and effectiveness of these treatments in this specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for early-stage Hodgkin’s Lymphoma, which typically involves chemotherapy alone, this treatment combines surgery, chemotherapy, and targeted radiotherapy. Researchers are excited because this approach aims to maximize cancer cell elimination while potentially reducing long-term side effects. The innovative aspect here is the use of involved-field radiotherapy (IFRT) following chemotherapy, which specifically targets remaining cancerous areas, potentially increasing the chances of complete remission. This comprehensive approach could offer a more effective and personalized treatment plan for patients.

What evidence suggests that this trial's treatments could be effective for early-stage Hodgkin's Lymphoma?

Research has shown that the combination of chemotherapy drugs used in this trial effectively treats early-stage Hodgkin's lymphoma, a cancer affecting lymph tissue. Participants will receive doxorubicin, vincristine, prednisone, and cyclophosphamide, which have improved survival rates. Specifically, doxorubicin and vincristine contributed to a 96% overall survival rate at 7 years for patients with stage I and II Hodgkin's lymphoma. Cyclophosphamide effectively treats various cancers, including lymphomas. Prednisone, when combined with other treatments, improves outcomes for early-stage Hodgkin's lymphoma. Participants who do not achieve a complete response after chemotherapy will receive radiation therapy, which can further enhance treatment success, as studies have shown high cure rates. Overall, these treatments have a strong history of improving patient outcomes for early-stage Hodgkin's lymphoma. ^{3 6 7 8 9}

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

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 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]

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK304336/

CYCLOPHOSPHAMIDE - Pharmaceuticals - NCBI Bookshelf Cyclophosphamide is used in the treatment of chronic lymphocytic leukaemia, lymphomas, soft tissue and osteogenic sarcoma, and solid tumours.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK553087/

Cyclophosphamide - StatPearls - NCBI Bookshelf - NIH Cyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer.

3. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/1361/480521/A-Retrospective-Analysis-of-the-Efficacy-of-Low

A Retrospective Analysis of the Efficacy of Low-Dose ... The overall best response rate (ORR) was 73.5% (12 complete responses, CRs and 13 partial responses, PRs), with 29.1 months of the median ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123129132

Prephase Cyclophosphamide: An Advantageous Bridge to ... In our analysis, pCy allowed 78% of patients to receive definitive therapy for their respective lymphoma. In general, patients receiving pCy required ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804911008252

Treatment outcome after low intensity chemotherapy [CVP ... Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/203856s003lbl.pdf

cyclophosphamide capsules - accessdata.fda.gov There is insufficient data from clinical studies of cyclophosphamide available for patients 65 years of age and older to determine whether they respond ...

7. go.drugbank.com go.drugbank.com/drugs/DB00531

Cyclophosphamide: Uses, Interactions, Mechanism of Action Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Modality: Small Molecule; Groups: Approved, Investigational; Structure. 3D.

8. medlineplus.gov medlineplus.gov/druginfo/meds/a682080.html

Cyclophosphamide: MedlinePlus Drug Information Cyclophosphamide is used alone or in combination with other medications to treat Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma.

9. elsevier.health elsevier.health/en-US/preview/cyclophosphamide

Cyclophosphamide NOTE: Cyclophosphamide is approved for the treatment of CLL[49678]; however, all components of combination regimens may not have been evaluated ...