Personalized Chemotherapy for Hodgkin's Lymphoma

Overseen By Hongyan Du, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Anti-cancer agents

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, 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: 12

Duration: 24 weeks

125 Participants Needed

Trial Summary

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 use other anti-cancer agents or experimental treatments while participating in this trial.

What data supports the effectiveness of the drug regimen for Hodgkin's Lymphoma?

The ABVD regimen, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, is a standard treatment for Hodgkin's lymphoma and has been shown to be effective in multiple studies. The inclusion of dacarbazine is crucial, as its absence leads to a significant loss of treatment effectiveness. ^{1 2 3 4 5}

Is personalized chemotherapy for Hodgkin's Lymphoma safe?

The treatments involving doxorubicin, vinblastine, and dacarbazine have been studied for Hodgkin's Lymphoma and are generally considered safe, though they can have side effects. Efforts have been made to reduce long-term side effects, especially in children, by adjusting the treatment combinations. ^{2 3 5 6 7}

How is the drug combination of Dacarbazine, Doxorubicin, Nivolumab, and Vinblastine unique for treating Hodgkin's Lymphoma?

This drug combination is unique because it includes Nivolumab, an immunotherapy drug that helps the immune system fight cancer, alongside traditional chemotherapy drugs like Dacarbazine, Doxorubicin, and Vinblastine, which are commonly used in standard regimens for Hodgkin's Lymphoma. ^{2 4 5 8 9}

What is the purpose of this trial?

This phase II trial tests how well personalized reduction of chemotherapy (nivolumab, doxorubicin, vinblastine and dacarbazine) based on circulating tumor deoxyribonucleic acid (ctDNA) evaluation works for treating patients with Hodgkin lymphoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Chemotherapy drugs, such as nivolumab, doxorubicin, vinblastine and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Many types of tumors tend to lose cells or release different types of cellular products including their DNA, which is referred to as ctDNA, into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids and, based on the result, assign patients to a reduced number of chemotherapy treatments or the standard number of chemotherapy treatments. Using ctDNA to assign a personalized reduction of chemotherapy may be effective in treating patients with advanced Hodgkin lymphoma.

Research Team

Ryan Lynch, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for patients with advanced Hodgkin lymphoma, where the cancer may have spread. Participants should be eligible for chemotherapy and willing to undergo various scans and provide biospecimens. Specific eligibility details are not provided.

Inclusion Criteria

I have stage 3 or 4 Hodgkin lymphoma and haven't received systemic therapy, but may have taken steroids for symptoms.

All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines

I agree to use barrier contraception during and for 120 days after the study.

Exclusion Criteria

Concurrent use of other anti-cancer agents or experimental treatments

I have not received a live vaccine in the last 30 days.

I've been cancer-free for 2+ years, except for certain skin, breast, or cervical cancers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab, doxorubicin, vinblastine, and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 6 cycles based on MRD status.

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for 1 year, then periodically for up to 5 years.

5 years

Periodic visits

Treatment Details

Interventions

• Dacarbazine
• Doxorubicin
• Nivolumab
• Vinblastine

Trial Overview The study tests personalized chemotherapy reduction based on ctDNA levels in blood. Patients receive nivolumab, doxorubicin, vinblastine, and dacarbazine. The goal is to see if fewer treatments can be as effective when ctDNA levels are low.

Participant Groups

Group I: Arm II (MRD positive) Experimental Treatment 10 Interventions

CYCLES 1-2: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo MRD testing. CYCLES 3-6: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 4 additional cycles (total of 6 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, PET/CT scan, questionnaire and blood sample collection throughout the study.

Group II: Arm I (MRD negative) Experimental Treatment 10 Interventions

CYCLES 1-2: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo MRD testing. CYCLES 3-4: Patients receive nivolumab IV, doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression of unacceptable toxicity. CYCLES 5-6: Patients receive nivolumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, PET/CT scan, questionnaire and blood sample collection throughout the study.

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

Approved in United States as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in European Union as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in Canada as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Findings from Research

In a study involving 807 patients with advanced Hodgkin's lymphoma, the standard treatment regimen ABVD showed similar event-free survival (EFS) and overall survival (OS) rates compared to two multidrug regimens (MDRs) over a median follow-up of 52 months, indicating that ABVD remains the preferred treatment option.

Patients receiving MDRs experienced more severe side effects, such as infections and mucositis, suggesting that while MDRs are not more effective than ABVD, they may pose additional risks, particularly for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). Johnson, PW., Radford, JA., Cullen, MH., et al.[2022]

The shortage of dacarbazine (DTIC) has significantly impacted the treatment of classical Hodgkin lymphoma, as it is a crucial part of the ABVD regimen, and removing it has previously resulted in reduced treatment effectiveness.

The review suggests alternative management strategies and a treatment algorithm based on patient fitness and safety for receiving anthracyclines, aiming to optimize care during the DTIC shortage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Strategies for Advanced Classical Hodgkin Lymphoma in the Times of Dacarbazine Shortage. Torka, P., Przespolewski, E., Evens, AM.[2022]

The OEPA chemotherapy regimen, which substitutes etoposide for procarbazine in boys with pediatric Hodgkin's disease, shows similar initial response rates to the traditional OPPA regimen, while potentially reducing the risk of testicular dysfunction.

With a 5-year event-free survival rate of 91% and overall survival rate of 98% across 578 patients, the study demonstrates that the DAL-HD-90 treatment approach effectively maintains high cure rates while minimizing long-term toxicity through reduced radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group. Schellong, G., Pötter, R., Brämswig, J., et al.[2022]

The ABOD regimen (doxorubicin, bleomycin, vincristine, and dacarbazine) demonstrated an 82.3% complete response rate in Hodgkin's lymphoma patients, indicating its efficacy even in those with unfavorable risk factors.

With a 5-year overall survival rate of 74% and manageable toxicity, ABOD appears to be a safe treatment option for Hodgkin's lymphoma, as no toxicity-related deaths were reported in the study of 79 patients over a median follow-up of 54 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first line vincristine with doxorubicin, bleomycin and dacarbazine (ABOD) for Hodgkin's lymphoma: a single institute experience. Ozdemir, N., Dogan, M., Sendur, MA., et al.[2019]

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]

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]

In a phase II trial involving 170 patients with early-stage unfavorable Hodgkin lymphoma, the combination of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) resulted in a higher PET-negative response rate (82.3%) after two cycles compared to the standard ABVD treatment (75.4%).

The 2-year progression-free survival (PFS) rate was also higher in the BV-AVD group (97.3%) compared to the ABVD group (92.6%), indicating that BV-AVD may offer a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. Fornecker, LM., Lazarovici, J., Aurer, I., et al.[2023]

In a study of 399 patients with limited-stage Hodgkin's lymphoma, those receiving radiation therapy in addition to ABVD chemotherapy had a higher 5-year freedom from disease progression (93%) compared to those receiving ABVD alone (87%).

Despite the improved disease progression outcomes with radiation therapy, there was no significant difference in overall survival between the two treatment groups, indicating that while radiation may help prevent disease recurrence, it does not necessarily extend life expectancy.

NCBI (Pubmed)

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. Meyer, RM., Gospodarowicz, MK., Connors, JM., et al.[2013]

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]

References

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

Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). [2022]

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

Treatment Strategies for Advanced Classical Hodgkin Lymphoma in the Times of Dacarbazine Shortage. [2022]

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

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group. [2022]

4. Thailand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first line vincristine with doxorubicin, bleomycin and dacarbazine (ABOD) for Hodgkin's lymphoma: a single institute experience. [2019]

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

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

6. 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]

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

Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. [2023]

8. 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]

9. United States 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. [2022]