Chemotherapy + Immunotherapy for Hodgkin's Lymphoma

Overseen By Ryan Lynch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must not be taking: Other anti-cancer agents

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of chemotherapy and immunotherapy to evaluate its effectiveness in treating classical Hodgkin lymphoma, a type of blood cancer. It tests the side effects and effectiveness of four drugs: doxorubicin hydrochloride, pembrolizumab (an immunotherapy drug), vinblastine, and dacarbazine. The goal is to determine if these drugs together can more effectively stop the cancer from growing and spreading. Individuals who have not yet received treatment for classical Hodgkin lymphoma and have measurable disease might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether 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 a combination of chemotherapy drugs—doxorubicin hydrochloride, vinblastine, and dacarbazine—along with the immunotherapy drug pembrolizumab, is under study for safety in treating classical Hodgkin lymphoma. Previous studies have demonstrated that these chemotherapy drugs effectively stop cancer cells from growing by killing them or preventing their spread. Pembrolizumab aids the immune system in attacking cancer cells.

These treatments are being tested to assess patient tolerance. Studies with similar drug combinations have reported side effects, including nausea, tiredness, and low blood cell counts. However, these side effects are common with many chemotherapy treatments and can often be managed with medical care.

Notably, the FDA has already approved pembrolizumab for other conditions, indicating its safety for use in humans in different situations. This ongoing trial aims to better understand its safety when combined with these specific chemotherapy drugs for treating Hodgkin lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy and immunotherapy for Hodgkin's Lymphoma because it introduces pembrolizumab, an immunotherapy drug, into the treatment regimen. Unlike traditional chemotherapy alone, which targets cancer cells directly, pembrolizumab works by enabling the immune system to recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses while using tried-and-true chemotherapy agents like doxorubicin, vinblastine, and dacarbazine. By integrating these mechanisms, the treatment has the potential to improve outcomes and offer new hope for patients with Hodgkin's Lymphoma.

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

In this trial, participants will receive a combination of drugs that have shown promise in treating Hodgkin's lymphoma. Dacarbazine, a chemotherapy drug, stops cancer cells from growing and is often used with other treatments for this disease. Doxorubicin hydrochloride, another chemotherapy drug, has been linked to high survival rates when combined with other treatments. Pembrolizumab, an immunotherapy drug, has effectively shrunk tumors and improved survival rates in patients who did not respond well to other treatments. Vinblastine, also a chemotherapy drug, is known for its effectiveness and relatively lower side effects in treating Hodgkin's lymphoma. Together, these drugs work to kill cancer cells and prevent them from spreading, offering hope for better patient outcomes. ^{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 untreated classical Hodgkin lymphoma. Eligible participants include those who are not pregnant, agree to use birth control, have a good performance status (able to carry out daily activities), and adequate organ function. It's not open to individuals with severe heart conditions, active infections, other cancers (except certain skin or in situ cancers), HIV/hepatitis B/C, or those on oxygen therapy.

Inclusion Criteria

My hemoglobin level is at least 8 g/dL.

My kidney function is within the required range.

Absolute neutrophil count (ANC) >= 1,500/mm^3 (without transfusion or growth factor support)

Exclusion Criteria

I am not pregnant or nursing and will use effective birth control if I can have children.

I do not have severe health issues that would prevent me from receiving strong chemotherapy.

I have had cancer before, but it was either skin cancer treated successfully, breast or cervical cancer that did not spread, or any cancer I've been free from for over 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Patients receive doxorubicin hydrochloride, vinblastine, and dacarbazine IV on days 1 and 15, and pembrolizumab IV on days 1 and 22 of cycle 1 and on day 15 of cycle 2. Treatment repeats every 28 days for up to 2 cycles.

8 weeks

Treatment Part B

Patients receive doxorubicin hydrochloride, vinblastine, dacarbazine, and pembrolizumab IV as in Part A, but undergo a total of 6 treatment cycles.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then up to 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dacarbazine
• Doxorubicin Hydrochloride
• Pembrolizumab
• Vinblastine

Trial Overview

The study tests the effectiveness of combining chemotherapy drugs doxorubicin hydrochloride, vinblastine, dacarbazine with immunotherapy drug pembrolizumab in treating Hodgkin lymphoma. The goal is to see if this combination helps stop cancer cells from growing by killing them directly or disrupting their spread.

How Is the Trial Designed?

Group I: Treatment (APVD) Experimental Treatment 5 Interventions

PART A: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine IV, and dacarbazine IV on days 1 and 15. Patients also receive pembrolizumab IV over 30 minutes on days 1 and 22 of cycle 1 and on day 15 of cycle 2. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. PART B: Patients receive doxorubicin hydrochloride IV, vinblastine IV, dacarbazine IV, and pembrolizumab IV as in part A, but undergo a total of 6 treatment cycles.

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

In a phase II study of 39 patients with relapsed or refractory classical Hodgkin lymphoma, the combination of pembrolizumab with gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) resulted in a remarkable overall response rate of 100% and a complete response rate of 95%.

The treatment was well-tolerated, with most adverse events being mild (grade 1 or 2), and 95% of patients successfully proceeded to high-dose therapy and autologous hematopoietic cell transplantation, with all transplanted patients remaining in remission at a median follow-up of 13.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. Moskowitz, AJ., Shah, G., Schöder, H., et al.[2023]

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]

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 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 the ECHELON-1 study involving 1334 patients with stage III or IV classical Hodgkin lymphoma, the A+AVD treatment (brentuximab vedotin combined with standard chemotherapy) demonstrated a significantly better 5-year progression-free survival rate of 82.2% compared to 75.3% for the ABVD treatment, indicating its superior efficacy.

The safety profile of A+AVD was consistent, with fewer secondary malignancies reported compared to ABVD, and while more patients experienced ongoing peripheral neuropathy with A+AVD, the condition improved over time, suggesting a manageable side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Straus, DJ., Długosz-Danecka, M., Connors, JM., et al.[2022]

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