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

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

82 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nivolumab in combination with other treatments for Hodgkin's Lymphoma?

Nivolumab, an immunotherapy drug, has shown effectiveness in treating other cancers, such as malignant pleural mesothelioma, when combined with other treatments. Although the research does not directly address Hodgkin's Lymphoma, the success of Nivolumab in combination therapies for other cancers suggests potential benefits for similar approaches in Hodgkin's Lymphoma. ^{1 2 3 4 5}

Is the ABVD treatment generally safe for Hodgkin's Lymphoma?

ABVD treatment, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, is generally used for Hodgkin's Lymphoma, but it can cause lung problems, especially in older patients, with 24% experiencing lung toxicity and some cases leading to death. ^{6 7 8 9 10}

What makes the A(B)VD + Nivolumab drug unique for treating Hodgkin's Lymphoma?

The A(B)VD + Nivolumab treatment is unique because it combines the standard ABVD chemotherapy regimen with Nivolumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells. This combination aims to enhance the effectiveness of treatment by leveraging both chemotherapy and the body's immune response. ^{6 7 8 10 11}

What is the purpose of this trial?

This trial tests if adding Nivolumab to standard chemotherapy (ABVD) can improve cure rates for high-risk Hodgkin lymphoma patients. It targets those with advanced stages of the disease who haven't been treated yet. Nivolumab helps the immune system fight cancer, while ABVD kills cancer cells. Nivolumab is well tolerated and highly effective in relapsed/refractory classic Hodgkin lymphoma but has not been adequately studied in patients who are receiving their initial treatment for this type of cancer.

Research Team

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

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

2. Japan pubmed.ncbi.nlm.nih.gov

[Systemic Treatment of Malignant Pleural Mesothelioma]. [2020]

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

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Malignant Pleural Mesothelioma. [2020]

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. England pubmed.ncbi.nlm.nih.gov

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

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. [2021]

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

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

11. 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]