Immunotherapy for Hodgkin's Lymphoma

Not currently recruiting at 106 trial locations

Overseen By Toll Free Number

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: Organ transplant, Autoimmune 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

Duration: 8-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for children and young adults with classical Hodgkin Lymphoma (cHL) who haven't responded quickly to initial chemotherapy. It examines the safety and effectiveness of the drug pembrolizumab (an immunotherapy) when combined with different chemotherapy drugs. The trial includes two groups: one receives pembrolizumab with a mix called AVD, and the other with COPDAC-28. Those newly diagnosed with Hodgkin Lymphoma that hasn't spread extensively and who can still perform daily activities might be suitable candidates. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of pembrolizumab.

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

Research has shown that pembrolizumab, used in this trial, has been tested for safety in people with Hodgkin's lymphoma. In previous studies, about 5% of patients stopped taking pembrolizumab due to side effects, and 26% paused treatment because of them. This indicates that while some experience side effects, many continue treatment successfully.

The AVD chemotherapy regimen is a well-established treatment for Hodgkin's lymphoma. It includes drugs like doxorubicin, vinblastine, and dacarbazine, which have been safely used in many patients, making them a reliable option.

The COPDAC-28 regimen, another chemotherapy option in this trial, combines cyclophosphamide, vincristine, prednisone, and dacarbazine. Research suggests it may benefit those with Hodgkin's lymphoma and is generally considered safe.

Overall, while there is a risk of side effects, these treatments have been used in many patients and are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Hodgkin's Lymphoma because they incorporate pembrolizumab, an immunotherapy drug that works differently from traditional chemotherapy. Unlike standard treatments like ABVD or BEACOPP, which rely solely on chemotherapy to kill cancer cells, pembrolizumab helps the immune system recognize and attack cancer cells. In Group 1, pembrolizumab is combined with AVD chemotherapy, while in Group 2, it's paired with COPDAC-28 chemotherapy, offering a new approach that could enhance treatment effectiveness and reduce side effects. By using the body's own immune response, these treatments have the potential to improve outcomes for patients with Hodgkin's Lymphoma.

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

Research has shown that pembrolizumab, one of the treatments in this trial, yields promising results for treating classical Hodgkin Lymphoma (cHL) when combined with chemotherapy. In earlier studies, pembrolizumab alone effectively shrank tumors, with 69% of patients responding to the treatment. Specifically, 47% of patients experienced a partial reduction in their cancer. The drug enhances the immune system's ability to detect and fight cancer cells. While cHL often has a high cure rate, pembrolizumab offers additional hope for those who do not respond well to initial treatments. In this trial, participants will receive pembrolizumab alongside different chemotherapy regimens, potentially improving treatment outcomes for cHL. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for children and young adults with classical Hodgkin Lymphoma who are slow to respond to initial chemotherapy. They must have measurable disease, adequate organ function, and agree to specific contraception if applicable. Exclusions include severe allergies to study drugs, certain heart conditions, prior treatments with similar agents or vaccines close to the start of the trial, active infections like HIV or hepatitis, and other health issues that could interfere.

Inclusion Criteria

I have been newly diagnosed with early-stage classical Hodgkin Lymphoma without bulky disease.

I have been newly diagnosed with advanced Hodgkin lymphoma.

I am a male and agree to not donate sperm and follow the study's rules on sexual activity and contraception.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

I have had a solid organ transplant or a bone marrow transplant in the last 5 years.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive two 4-week cycles of ABVD or OEPA induction therapy

8 weeks

Treatment

Participants receive pembrolizumab in combination with AVD or COPDAC-28 chemotherapy

8-16 weeks

Radiotherapy

Participants receive radiotherapy based on PET scan results after chemotherapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Bleomycin
• Cyclophosphamide
• Dacarbazine
• Doxorubicin
• Etoposide
• Pembrolizumab
• Prednisone/Prednisolone
• Vinblastine
• Vincristine

Trial Overview The trial tests pembrolizumab combined with standard chemotherapy in patients who haven't responded well initially. It aims to see how safe this combination is and how effective it is at treating Hodgkin Lymphoma in these particular patients.

How Is the Trial Designed?

Group I: Pembrolizumab + COPDAC-28 (Group 2) Experimental Treatment 8 Interventions

After receiving two 4-week cycles of OEPA (vincristine, etoposide/etopophos, prednisone/prednisolone and doxorubicin) induction therapy, SER participants in Group 2 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 chemotherapy (cyclophosphamide 500 mg/m\^2 on Days 1 and 8, vincristine 1.5 mg/m\^2 with maximum single dose 2 mg on Days 1 and 8, prednisone/prednisolone 40 mg/m\^2/day divided in 3 doses on Days 1 to 15, dacarbazine 250 mg/m\^2 on Days 1 to 3; cycle frequency Q4W). SERs in Group 2 will receive RT if they have a positive Positron Emission Tomography (PET) response after completing COPDAC-28 chemotherapy.

Group II: Pembrolizumab + AVD (Group 1) Experimental Treatment 6 Interventions

After receiving two 4-week cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) induction therapy, SER participants in Group 1 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) on Day 1 of each 3-week cycle (Q3W) in combination with two cycles of AVD chemotherapy (doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2 and dacarbazine 375 mg/m\^2 on Days 1 and 15; cycle frequency every 4 weeks \[Q4W\]). All SERs in Group 1 will receive radiotherapy (RT) after completing AVD chemotherapy.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 222 patients with advanced Hodgkin lymphoma, the relative tumor burden (rTB) was identified as the best predictor of early treatment failures, indicating its importance in assessing treatment outcomes.

Patients treated with the BEACOPP chemotherapy regimen showed about half the risk of chemoresistance compared to those treated with ABVD, suggesting that BEACOPP may be more effective in curing patients with higher initial tumor burdens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoresistance as a function of the pretherapy tumor burden and the chemotherapy regimen administered: differences observed with 2 current chemotherapy regimens for advanced Hodgkin lymphoma. Gobbi, PG., Valentino, F., Bassi, E., et al.[2011]

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]

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]

In a study involving 856 adult patients with advanced Hodgkin's disease, both ABVD and MOPP/ABV regimens showed similar rates of complete remission and overall survival, indicating their effectiveness as initial chemotherapy treatments.

However, MOPP/ABV was associated with higher rates of acute pulmonary and hematologic toxicities, as well as a greater incidence of myelodysplastic syndromes (MDS) and leukemia, suggesting that ABVD is the safer and preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. Duggan, DB., Petroni, GR., Johnson, JL., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10602819/

Effectiveness and Safety of Pembrolizumab in Recurrent and ... Although there is currently a high cure rate for cHL, up to 30% of patients in the advanced stages and 5-10% of those in the limited stage ...

2. ashpublications.org ashpublications.org/blood/article/142/10/878/496370/Five-year-follow-up-of-KEYNOTE-087-pembrolizumab

Five-year follow-up of KEYNOTE-087: pembrolizumab ... Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05008224

NCT05008224 | Study of Safety and Efficacy ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab ...

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda-classical-hodgkin-lymphoma

Pembrolizumab (KEYTRUDA) for classical Hodgkin ... With a median follow-up of 9.4 months (range: 1-15), the overall response rate was 69% (95% CI: 62, 75). This included partial responses in 47% ...

5. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.10000

Updated safety and efficacy data from an open-label ... In phase 1, eight patients were treated with 48 mg/m2 of brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (AVD).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8247884/

Brentuximab vedotin plus doxorubicin, vinblastine, and ... Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years.

8. ashpublications.org ashpublications.org/blood/article/145/3/290/526323/Brentuximab-vedotin-nivolumab-doxorubicin-and

Brentuximab vedotin, nivolumab, doxorubicin, and ... Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02355

Nivolumab and Doxorubicin, Vinblastine, and Dacarbazine ... Two schedules of four cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine followed by 30 Gy involved-site radiotherapy resulted in high complete ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10864874/

Safety, efficacy, and affordability of ABVD for Hodgkin ... ABVD (doxorubicin, bleomycin, vinblastine, and dexamethasone) is a proven, curative regimen for Hodgkin lymphoma (HL). Prospective data ...