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

50 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination used in the Chemotherapy + Immunotherapy for Hodgkin's Lymphoma trial?

Research shows that a similar drug combination, including doxorubicin, vinblastine, and dacarbazine, has been effective in treating advanced Hodgkin's lymphoma, with some patients achieving long-term remission. Additionally, pembrolizumab, part of the trial's drug combination, has shown promise in treating relapsed Hodgkin's lymphoma when combined with other chemotherapy drugs. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy safe for treating Hodgkin's Lymphoma?

The safety of chemotherapy drugs like doxorubicin, vinblastine, and dacarbazine, often used in combination treatments for Hodgkin's Lymphoma, has been evaluated in several studies. These studies generally show that while these drugs can be effective, they may also cause side effects, which are common in cancer treatments. It's important to discuss potential risks and benefits with your healthcare provider. ^{1 4 6 7 8}

How is the chemotherapy and immunotherapy drug combination for Hodgkin's Lymphoma unique?

This treatment combines chemotherapy drugs (Dacarbazine, Doxorubicin, Vinblastine) with an immunotherapy drug (Pembrolizumab), which is unique because it leverages the body's immune system to help fight cancer cells, potentially offering a new approach compared to traditional chemotherapy regimens alone. ^{1 9 10 11 12}

What is the purpose of this trial?

This phase II trial studies the side effects of doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine in treating patients with classical Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with pembrolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.

Research Team

Ryan Lynch, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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]

References

1. 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]

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

Twenty-year disease and treatment-associated mortality rates of patients with Hodgkin lymphoma of clinical stages IIIB and IV prospectively treated with 3-month anthracycline-based chemotherapy followed by extended high-dose radiation. [2013]

3. United States 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. [2023]

4. 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]

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

Treatment of MOPP-refractory Hodgkin's disease with vinblastine, doxorubicin, bleomycin, CCNU, and dacarbazine. [2019]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2022]

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

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group. [2017]

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

Six cycles of ABVD in the treatment of stage I and II Hodgkin's lymphoma: a pilot study. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study. [2022]

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

Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B. [2017]