Pembrolizumab + Chemotherapy for Hodgkin's Lymphoma

Recruiting at 5 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, CNS metastases, Autoimmune, 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: 8

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on systemic steroid therapy or any other form of immunosuppressive therapy, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab combined with chemotherapy for treating Hodgkin's Lymphoma?

Research shows that the combination of doxorubicin, vinblastine, and dacarbazine (part of the ABVD regimen) is effective for treating Hodgkin's Lymphoma. This suggests that adding Pembrolizumab, which is known to enhance the immune system's ability to fight cancer, could potentially improve treatment outcomes. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and chemotherapy safe for humans?

The safety data for similar chemotherapy treatments, like those involving doxorubicin, show common side effects such as low white blood cell counts (leukopenia), low platelet counts (thrombocytopenia), nausea, vomiting, and hair loss. These side effects are generally manageable with medical support. ^{6 7 8 9 10}

What makes the drug combination of Pembrolizumab and chemotherapy unique for treating Hodgkin's Lymphoma?

This treatment combines Pembrolizumab, an immune checkpoint inhibitor that blocks a protein called PD-1 to help the immune system attack cancer cells, with chemotherapy drugs like Dacarbazine, Doxorubicin, and Vinblastine. This combination is unique because it targets the cancer in multiple ways, potentially improving response rates and offering a new option for patients who have not responded to other treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

This phase II trial tests how well giving pembrolizumab followed by chemotherapy with doxorubicin, vinblastine and dacarbazine works to treat patients with classical Hodgkin lymphoma. Pembrolizumab is a type of drug called a "monoclonal antibody (mAb)" that uses the body's immune system to help fight and kill cancer cells. Chemotherapy drugs, such as doxorubicin, 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. Giving pembrolizumab followed by chemotherapy may work to treat patients with classical Hodgkin lymphoma.

Research Team

Jane N. Winter, MD

Principal Investigator

Northwestern University

Eligibility Criteria

Adults with untreated classical Hodgkin lymphoma, stages I-IV, who are in good physical condition (ECOG 0-1) and have proper organ function. They must not be pregnant or breastfeeding, agree to use contraception, and have no history of severe allergies to trial drugs or similar compounds. Excluded are those with prior treatments for cHL, active CNS metastases, other cancers requiring treatment, uncontrolled illnesses or infections.

Inclusion Criteria

My cancer shows up on special PET scans.

My hemoglobin level is at least 8 g/dL.

Platelets (PLT) ≥ 25,000/mcL unless attributed to neoplastic involvement of the bone marrow

Exclusion Criteria

Patients who have had an allogenic tissue or solid organ transplant

Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, and/or any of its excipients

Patients who have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are not eligible

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive pembrolizumab intravenously over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity.

9 weeks

3 visits (in-person)

Consolidation

Patients receive doxorubicin, vinblastine, and dacarbazine intravenously on days 1 and 15 of each cycle. Cycles repeat every 28 days for 2 to 6 cycles depending on response and disease type.

8-24 weeks

4-12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 30 days, every 3 months for 1 year, and every 6 months for 4 years.

5 years

Multiple visits (in-person)

Treatment Details

Interventions

• Dacarbazine
• Doxorubicin
• Pembrolizumab
• Vinblastine

Trial Overview The trial is testing the effectiveness of pembrolizumab (a monoclonal antibody that activates the immune system against cancer cells) followed by chemotherapy drugs doxorubicin, vinblastine and dacarbazine in treating patients with classical Hodgkin lymphoma.

Participant Groups

Group I: Treatment (Pembrolizumab and AVD) Experimental Treatment 10 Interventions

INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessment. Patients with a response complete 3 additional cycles of pembrolizumab, undergo disease assessment and proceed to consolidation. Patients without response or with progressive disease proceed to consolidation. CONSOLIDATION: Patients receive doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for 2 to 6 cycles dependent upon response and disease type. Patients undergo echocardiography/MUGA scan, CT scan, PET scan and blood sample collection throughout the study and may undergo tumor biopsy during screening.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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 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]

L-histidinol protects normal MDCK epithelial cells from daunomycin (DAU) toxicity while increasing toxicity in the tumorigenic MDCK-T1 cells, indicating a selective modulation of drug effects based on cell type.

Imidazole was found to be as effective as L-histidinol in protecting MDCK cells from DAU, but had a lesser effect on the tumorigenic cells, suggesting that the protective mechanism may involve both inhibition of protein synthesis and additional actions related to its chemical structure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mimetics of L-histidinol which selectively modulate daunomycin toxicity in normal and tumorigenic epithelial cells. Warrington, RC., Fang, WD., Zhang, L., et al.[2013]

In a late phase II clinical trial involving 39 patients with non-Hodgkin's lymphoma, amrubicin hydrochloride demonstrated a high efficacy rate, achieving a complete response (CR) or unconfirmed complete response (CRu) in 70.3% of patients and an overall response rate of 86.5%.

While amrubicin hydrochloride was effective, it was associated with significant adverse reactions, particularly myelosuppression, with 100% of patients experiencing leukopenia and neutropenia, though these were manageable with supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma]. Akutsu, M., Kano, Y., Ogawa, M., et al.[2015]

SC-33428, a new drug similar to doxorubicin, showed stronger bone marrow suppression in rats compared to doxorubicin, but had less harmful effects on the heart and kidneys.

The lower concentrations of SC-33428 in the body after administration suggest it may have a better safety profile than doxorubicin while maintaining similar effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological studies with a novel synthetic anthracycline, the bis-hydrazone bridged analog of 4-demethoxydaunorubicin (SC-33428). Zbinden, G., Beilstein, AK., Bachmann, E.[2013]

Rubidazone, tested in 33 patients with advanced solid tumors or malignant lymphomas, showed only modest antitumor effects, with partial remission in one patient and stable disease in seven others for 4-18 weeks.

The treatment was associated with significant side effects, including gastrointestinal issues, myelosuppression, and in some cases, cardiac toxicity and anaphylactic-like reactions, indicating a need for careful monitoring during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of rubidazone in solid tumors and malignant lymphomas. Skovsgaard, T., Hansen, HH., Mouridsen, HT., et al.[2019]

In a phase II study involving 36 patients with malignant lymphoma, amrubicin hydrochloride showed an overall response rate of 50% for Hodgkin's disease and 42.9% for non-Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The treatment was associated with significant side effects, including severe leukopenia in 58.3% of patients and thrombocytopenia in 27.8%, highlighting the need for careful monitoring of blood cell counts during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma]. Masaoka, T., Ogawa, M., Inoue, K., et al.[2012]

In a phase II study involving 210 patients with relapsed or refractory classic Hodgkin lymphoma, pembrolizumab showed a high overall response rate of 69%, indicating its effectiveness as a treatment option.

The safety profile of pembrolizumab was consistent with previous studies, suggesting it is a well-tolerated therapy for patients with this challenging form of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. Chen, R., Zinzani, PL., Fanale, MA., et al.[2022]

Chemotherapy for classic Hodgkin lymphoma patients on hemodialysis is complex due to the risk of both overdose and undertreatment, necessitating careful dose modifications and timing of drug administration in relation to dialysis sessions.

This review provides practical recommendations for administering various chemotherapeutics, including ABVD and PD-1 inhibitors, based on a comprehensive literature review of treatment experiences in this unique patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hodgkin Lymphoma on Hemodialysis: A Review of Treatment and Recommendations. Yasuda, H., Komatsu, N., Ando, J., et al.[2022]

In a study of 30 patients with untreated classic Hodgkin lymphoma, the combination of pembrolizumab with chemotherapy (AVD) demonstrated a 100% overall response rate and a 90% complete response rate, indicating high efficacy.

The treatment was generally safe, with no significant delays in administration; however, some patients experienced serious adverse events, including febrile neutropenia and immune-related effects, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Lynch, RC., Ujjani, CS., Poh, C., et al.[2023]

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 patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

References

1. 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]

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

Treatment Strategies for Advanced Classical Hodgkin Lymphoma in the Times of Dacarbazine Shortage. [2022]

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Greece pubmed.ncbi.nlm.nih.gov

Mimetics of L-histidinol which selectively modulate daunomycin toxicity in normal and tumorigenic epithelial cells. [2013]

7. Japan pubmed.ncbi.nlm.nih.gov

[Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma]. [2015]

8. Germany pubmed.ncbi.nlm.nih.gov

Toxicological studies with a novel synthetic anthracycline, the bis-hydrazone bridged analog of 4-demethoxydaunorubicin (SC-33428). [2013]

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

Clinical trial of rubidazone in solid tumors and malignant lymphomas. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

[Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma]. [2012]

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

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. [2022]

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

Hodgkin Lymphoma on Hemodialysis: A Review of Treatment and Recommendations. [2022]

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

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. [2023]

14. 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]

15. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. [2019]