A(B)VD + Nivolumab for Hodgkin's Lymphoma

Not currently recruiting at 9 trial locations

Overseen By Heiko Schoder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: ABVD

Must not be taking: Systemic corticosteroids

Disqualifiers: Brain metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding Nivolumab, an immunotherapy drug, to the standard ABVD treatment can improve the chances of curing Hodgkin's lymphoma, a type of blood cancer. For individuals not yet treated, the trial will test various combinations of these drugs to assess their effectiveness and safety. The trial seeks participants diagnosed with untreated Hodgkin's lymphoma, especially those with advanced stages of the disease or abnormal PET scan results after starting treatment. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids, you may need to taper them down to 10mg or less by 4 weeks after starting the trial treatment.

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

Research shows that nivolumab, one of the treatments in this trial, is generally well-tolerated by people with Hodgkin's lymphoma. Studies have demonstrated that it can lead to strong and lasting improvements in patients whose cancer has returned or resisted other treatments. For example, one study found that when nivolumab was used with the AVD chemotherapy drugs, 88% of patients did not see their cancer worsen for at least two years. This suggests that the combination is effective and safe for many patients.

The ABVD chemotherapy regimen, which includes drugs like bleomycin, dacarbazine, doxorubicin, and vinblastine, is already approved by the FDA for treating Hodgkin's lymphoma. This approval indicates that its safety is well-understood. While side effects can occur, this regimen is widely used and considered safe for many people.

In summary, both nivolumab and the ABVD regimen have been studied for their safety and effectiveness in treating Hodgkin's lymphoma. Prospective participants can find reassurance in these findings. However, as with any treatment, side effects may occur, and discussing these with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining A(B)VD with Nivolumab for treating Hodgkin's Lymphoma because it introduces an innovative approach to tackling the disease. Unlike traditional treatments that rely solely on chemotherapy agents like Bleomycin, Dacarbazine, Doxorubicin, and Vinblastine, this regimen includes Nivolumab, an immunotherapy drug. Nivolumab works by harnessing the body's immune system to target and destroy cancer cells, offering a novel mechanism of action compared to standard chemotherapy. This combination has the potential to enhance treatment efficacy and improve patient outcomes by integrating the body's natural defenses with established chemotherapy protocols.

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

Research shows that combining Nivolumab with the AVD treatment plan (which includes doxorubicin, vinblastine, and dacarbazine) holds promise for treating Hodgkin's Lymphoma. In this trial, participants under 60 with advanced-stage Hodgkin's Lymphoma will receive Nivolumab with AVD during cycle 6, while those 60 and older will receive it during cycles 5 and 6. One study found that 88% of patients maintained stable cancer without worsening for two years, marking one of the best outcomes for advanced stages of the disease. Nivolumab alone has also produced good results in difficult-to-treat or recurrent Hodgkin's cases, with some patients experiencing complete tumor disappearance. The ABVD treatment plan, which includes bleomycin, has historically achieved long-lasting responses in 85% of patients. This new combination aims to further improve these outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with untreated classical Hodgkin lymphoma who are at higher risk (stage III or IV, or positive PET scans after initial treatment). It's open to those under 60 for one cohort and over 60 for another. Participants need functioning major organs, not be pregnant or breastfeeding, and must use reliable birth control.

Inclusion Criteria

FDG-avid disease by FDG-PET/CT

I am 60 or older with untreated classical Hodgkin lymphoma.

I agree to use contraception during and for 31 weeks after treatment if I'm sexually active with a woman who can become pregnant.

Exclusion Criteria

I haven't had serious heart issues in the last 6 months.

My heart's pumping ability is below normal.

I do not have uncontrolled heart problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 cycles of A(B)VD and nivolumab, with PET scans to assess response

6 months

Regular visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bleomycin
• Dacarbazine
• Doxorubicin
• Nivolumab
• Vinblastine

Trial Overview

The study is testing the effectiveness of Nivolumab combined with a chemotherapy regimen called ABVD (which includes dacarbazine, doxorubicin, bleomycin, vinblastine) as a first-line treatment to see if it can improve cure rates in patients with high-risk Hodgkin lymphoma.

How Is the Trial Designed?

Group I: < 60 years of age with advanced stage (HL) untreated Experimental Treatment 5 Interventions

The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of A(B)VD and 8 doses of nivolumab. In dose level 1, patients will receive nivolumab in combination with AVD during cycle 6 only followed by 6 additional doses of nivolumab. In subsequent dose levels, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3. A PET scan will be performed after 2 cycles of ABVD and those with a PET-negative response (defined by Deauville 1, 2 or 3) will proceed with 4 additional cycles of ABVD or AVD (per treating physician preference).

Group II: 60 years of age and older with HL (any stage) untreated Experimental Treatment 4 Interventions

The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of AVD and 12 doses of nivolumab. In this cohort, patients will receive nivolumab in combination with AVD during cycles 5 and 6 only, followed by 8 additional doses of nivolumab. In subsequent cohorts, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3. Prophylactic growth factor support is mandatory for all patients on Cohort B and should be used per the treating physician's discretion for all other patients.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

British Columbia Cancer Agency

Collaborator

Trials

181

Recruited

95,900+

Barbara Ann Karmanos Cancer Institute

Collaborator

Trials

166

Recruited

9,300+

Published Research Related to This Trial

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]

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.

The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Wright, K.[2021]

Current standard treatment for malignant pleural mesothelioma (MPM) involves platinum-based chemotherapy with pemetrexed, but immunotherapy has shown limited efficacy, with PD-(L)1 inhibitors yielding response rates of only 10-29% in phase II trials.

Recent studies indicate that single-agent immunotherapies like pembrolizumab do not outperform traditional chemotherapy, highlighting the need for better biomarkers to identify which patients might benefit from immunotherapy and the potential of combining immunotherapy with chemotherapy for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Malignant Pleural Mesothelioma. de Gooijer, CJ., Borm, FJ., Scherpereel, A., et al.[2020]

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 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]

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 study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

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