Pembrolizumab + Stem Cell Transplant for Hodgkin's Lymphoma

Overseen By Roberta Nicklow

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Corticosteroids, Autoimmune agents

Disqualifiers: Autoimmune disease, CNS disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2 single arm study to evaluate efficacy and safety of Pembrolizumab before with BEAM ASCT followed by Pembrolizumab maintenance for 1 year. Patients will receive 200 mg Pembrolizumab Q3week starting at day - 28 before stem cell transplant until 1 year after autologous stem cell transplant.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy within 3 weeks before starting the study, and certain vaccines and steroids are restricted. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab in treating Hodgkin's Lymphoma?

Research shows that pembrolizumab, when used after stem cell transplants, can significantly improve the time patients live without the disease getting worse, with 82% of patients not experiencing disease progression 18 months after treatment. This suggests pembrolizumab is effective in treating relapsed or refractory Hodgkin's Lymphoma. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and stem cell transplant safe for treating Hodgkin's Lymphoma?

Pembrolizumab has been shown to have a favorable safety profile in patients with Hodgkin's Lymphoma, with some experiencing manageable side effects. In studies, a small percentage of patients had severe side effects, but there were no treatment-related deaths. ^{1 2 4 6 7}

How is the drug pembrolizumab used in treating Hodgkin's Lymphoma different from other treatments?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, which is particularly effective in Hodgkin's Lymphoma. It is used after stem cell transplants to improve outcomes by preventing relapse, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 8 9}

Eligibility Criteria

This trial is for individuals with relapsed Hodgkin Lymphoma who are eligible for an autologous stem cell transplant (ASCT) using the BEAM conditioning regimen. Participants must have well-controlled HIV or HCV if present, good performance status (KPS > 70 or ECOG ≤ 1), adequate organ function and blood counts, and undetectable HBV viral load if they are HBsAg positive.

Inclusion Criteria

My organs are working well and my blood counts are normal.

I am eligible for a stem cell transplant with specific pre-transplant therapy.

I am mostly self-sufficient and can carry out daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Treatment

Participants receive 200 mg Pembrolizumab every 3 weeks starting at day -28 before stem cell transplant

4 weeks

Stem Cell Transplant

Participants undergo BEAM conditioning regimen followed by autologous stem cell transplant

1 week

Maintenance Treatment

Participants receive Pembrolizumab maintenance therapy for 1 year post-transplant

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Carmustine, Etoposide, Cytarabine, Melphalan
• Pembrolizumab

Trial Overview The study tests Pembrolizumab's effectiveness and safety when given before and after ASCT with BEAM chemotherapy in patients with Hodgkin Lymphoma. Patients will receive Pembrolizumab every three weeks starting from one month before until one year after their stem cell transplant.

Participant Groups

Group I: Pembrolizumab+BEAM followed by ASCT followed by Pembrolizumab maintenance for 1 year. Experimental Treatment 6 Interventions

Patients will receive Pembrolizumab before BEAM ASCT followed by Pembrolizumab maintenance for 1 year. Patients will receive 200 mg Pembrolizumab starting at day - 28 before stem cell transplant until 1 year after autologous stem cell transplant.

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

In a study of 55 patients with relapsed/refractory Hodgkin's Lymphoma, Pembrolizumab showed a high response rate of 74.5%, with a complete response in 32.7% of patients, indicating its efficacy before autologous stem cell transplantation.

The 12-month overall survival rate was 92%, and the progression-free survival rate was 51%, demonstrating reasonable safety and promising survival outcomes for patients treated with checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. Halahleh, K., Al Sawajneh, S., Saleh, Y., et al.[2022]

In a phase 2 study involving 30 patients with relapsed/refractory classical Hodgkin lymphoma (cHL), pembrolizumab given after autologous stem cell transplantation (ASCT) achieved an impressive 82% progression-free survival (PFS) at 18 months, surpassing the initial goal of 80%.

The treatment was well-tolerated, with manageable toxicity; 30% of patients experienced grade 3 or higher adverse events, and 40% had immune-related adverse events, indicating that pembrolizumab could be a safe consolidation option for high-risk patients post-ASCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. Armand, P., Chen, YB., Redd, RA., et al.[2023]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Monoclonal antibodies targeting the PD-1/PD-L1 axis, such as nivolumab and pembrolizumab, have shown significant efficacy in treating relapsed/refractory classical Hodgkin's lymphoma (cHL), leading to their FDA approval for this indication.

These therapies enhance the antitumor immune response by overcoming T cell exhaustion, and ongoing studies are exploring their safety and effectiveness in combination with other treatments, including allogeneic stem-cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its role in relapsed/refractory classical Hodgkin's lymphoma: evidence to date and clinical utility. Shindiapina, P., Alinari, L.[2023]

Checkpoint inhibitors like nivolumab and pembrolizumab are effective treatment options for patients with relapsed or refractory classic Hodgkin lymphoma, particularly for those who cannot undergo autologous stem-cell transplantation due to health issues.

These treatments not only improve overall survival rates but also have a manageable side effect profile, making them a safer alternative for patients with comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma. Al-Hadidi, SA., Lee, HJ.[2022]

In a phase Ib study involving 31 patients with relapsed or refractory Hodgkin lymphoma, pembrolizumab showed a favorable safety profile with only 16% experiencing grade 3 drug-related adverse events and no grade 4 adverse events or treatment-related deaths.

The treatment resulted in a 16% complete remission rate and a 65% overall response rate, with most responses lasting over 24 weeks, indicating that pembrolizumab may be an effective option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. Armand, P., Shipp, MA., Ribrag, V., et al.[2022]

Pembrolizumab has been approved by the FDA for treating classical Hodgkin lymphoma in both adults and children whose cancer has not responded to or has returned after at least three previous treatments.

This approval is significant as it is the first time a PD-1 inhibitor has been authorized for use in blood cancers, highlighting its potential as a new treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Hodgkin Lymphoma. [2018]

Pembrolizumab, an immune checkpoint inhibitor targeting the PD-1 pathway, significantly improves progression-free survival in patients with relapsed or refractory Classical Hodgkin lymphoma (cHL), particularly in those who have undergone autologous stem cell transplant or have chemotherapy-resistant disease.

While there is promising evidence for combining pembrolizumab with chemotherapy to enhance treatment efficacy, further large-scale randomized studies are necessary to confirm these benefits and to develop predictive biomarkers for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of pembrolizumab for classical Hodgkin lymphoma. Manji, F., Laister, RC., Kuruvilla, J.[2022]

In a phase 3 study involving 304 patients with relapsed or refractory classical Hodgkin lymphoma, pembrolizumab demonstrated a median progression-free survival of 13.2 months, significantly longer than the 8.3 months observed with brentuximab vedotin, indicating its superior efficacy.

While both treatments had associated adverse events, pembrolizumab's safety profile was consistent with previous studies, with serious treatment-related events occurring in 16% of patients, supporting its use as a preferred option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Kuruvilla, J., Ramchandren, R., Santoro, A., et al.[2021]

References

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

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. [2022]

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

PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its role in relapsed/refractory classical Hodgkin's lymphoma: evidence to date and clinical utility. [2023]

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

Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma. [2022]

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

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. [2022]

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

Pembrolizumab Approved for Hodgkin Lymphoma. [2018]

8. England pubmed.ncbi.nlm.nih.gov

An evaluation of pembrolizumab for classical Hodgkin lymphoma. [2022]

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

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. [2021]