Personalized Chemotherapy for Hodgkin's Lymphoma

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a personalized approach to chemotherapy for advanced Hodgkin lymphoma, a type of cancer that may have spread beyond its original area. The study aims to determine if adjusting chemotherapy based on tumor DNA levels in the blood can effectively treat the disease. Participants will receive a combination of drugs, including Dacarbazine, Doxorubicin, Nivolumab, and Vinblastine, with the number of treatment cycles depending on their specific tumor DNA results. This trial is particularly suited for those who haven't received systemic treatment for stage 3 or 4 Hodgkin lymphoma and have measurable disease. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to benefit from a potentially effective therapy.

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.

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

Research shows that the treatments in this trial—nivolumab, doxorubicin, vinblastine, and dacarbazine—are generally safe for Hodgkin lymphoma and similar conditions.

Studies indicate that nivolumab is usually well-tolerated by patients with classical Hodgkin lymphoma, though rare serious side effects like lung inflammation can occur. Overall, it has a good safety record.

Doxorubicin is also used for Hodgkin lymphoma. It can cause side effects such as heart damage, especially at high doses, but regular monitoring helps manage these risks.

Vinblastine, another chemotherapy drug for Hodgkin lymphoma, is generally well-tolerated but can lower blood cell counts and may cause nerve damage.

Dacarbazine, often used with other drugs, has a known safety profile for Hodgkin lymphoma. Common side effects include nausea and reduced blood cell counts.

These drugs have a history of use in cancer treatment, and past studies have shown that their safety is well-understood. While side effects can occur, they are usually manageable with medical care. ^{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 combine personalized chemotherapy with immunotherapy, offering a new approach compared to the standard ABVD regimen (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine). This trial uses a combination of Dacarbazine, Doxorubicin, Vinblastine, and Nivolumab, a drug that harnesses the immune system to fight cancer cells. By incorporating Nivolumab, an immune checkpoint inhibitor, the treatment aims to enhance the body's immune response against the cancer, potentially leading to better outcomes. Unlike traditional chemotherapy that targets all rapidly dividing cells, this approach aims to provide a more targeted attack on cancer cells, reducing potential side effects and improving patient quality of life.

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

This trial will evaluate a combination of four drugs—nivolumab, doxorubicin, vinblastine, and dacarbazine—for treating Hodgkin's lymphoma. Participants will be divided into two groups based on MRD status. Studies have shown that this combination effectively reduces swollen lymph nodes and improves symptoms like fever, night sweats, and weight loss. Research indicates that this treatment is generally well-tolerated and effective for various patient groups. Nivolumab, an immunotherapy drug in this combination, has shown promise in shrinking tumors and slowing the disease. These findings support the treatment's potential effectiveness for people with advanced Hodgkin's lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Ryan Lynch, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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.

Patients known positive for HIV or infectious hepatitis type B or C with a detectable viral load may not participate

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39661923/

Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine ... N-AVD is a highly effective and well-tolerated frontline regimen in OA with cHL across a wide range of geriatric impairments.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05675410

NCT05675410 | A Study to Compare Standard Therapy ... This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without ...

3. chemoexperts.com chemoexperts.com/nivolumab-opdivo-avd.html

Nivolumab (Opdivo®) + AVD (Doxorubicin + Vinblastine ... Nivolumab + AVD is given to shrink enlarged lymph nodes and decrease symptoms from Hodgkin's lymphoma such as fever, night sweats, and weight loss.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36508302/

Nivolumab and Doxorubicin, Vinblastine, and Dacarbazine ... Nivolumab and Doxorubicin, Vinblastine, and Dacarbazine in Early-Stage Unfavorable Hodgkin Lymphoma: Final Analysis of the Randomized German Hodgkin Study Group Phase II NIVAHL Trial. J Clin Oncol. 2023 Feb 20;41(6):1193-1199. doi: 10.1200/JCO.22.02355 ...

5. ncoda.org ncoda.org/pes/nivolumab-and-avd-doxorubicin-vinblastine-dacarbazine/

Nivolumab and AVD (Doxorubicin, Vinblastine, Dacarbazine) The combination of nivolumab and AVD (doxorubicin, vinblastine, darcarbazine) is used for Hodgkin lymphoma. Supported by: PES-Partnership ...

6. macmillan.org.uk macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/dacarbazine

Dacarbazine (chemotherapy drug) - treatment, side effects Dacarbazine (DTIC) is used to treat melanoma, Hodgkin lymphoma and soft tissue sarcoma. ... This is to check that it is safe for you to have chemotherapy.

7. goodrx.com goodrx.com/dacarbazine/what-is?srsltid=AfmBOoqAx7stsfLWM7oeCEnLwEPlDYsKmF9sa8rrwjN7B3-SYJgWo-VG

Dacarbazine: Uses, Side Effects, Dosage & More Hodgkin's lymphoma: The most common dose is 375 mg/m2 injected into the vein (IV) every 2 weeks. Metastatic melanoma: The recommended dose is 250 mg/m2 given IV ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK548913/

Dacarbazine - LiverTox - NCBI - NIH Current indications include Hodgkin lymphoma and metastatic malignant melanoma usually in combination with other antineoplastic agents.

9. empr.com empr.com/drug/dacarbazine/

Dacarbazine Prescription & Dosage Information - MPR Second-line therapy for Hodgkin's disease, in combination with other agents. Dacarbazine Dosage and Administration. Adult. Give by IV infusion. 150mg/m2 daily ...

10. bloodcancerunited.org bloodcancerunited.org/blood-cancer-care/cancer-drug-listing/dacarbazine

Dacarbazine Dacarbazine is used to treat people who have Hodgkin lymphoma as a second-line therapy when used in combination with other agents and is also used as ...