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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of Pembrolizumab with a stem cell transplant to determine its effectiveness in treating Hodgkin's Lymphoma, a type of cancer. The treatment involves administering Pembrolizumab before and after the transplant to assess its safety and effectiveness over a year. It suits individuals eligible for a specific type of stem cell transplant and those with conditions like well-controlled HIV or hepatitis. However, it is not suitable for individuals with active autoimmune diseases or recent chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that pembrolizumab is generally well-tolerated by patients. Studies have demonstrated that patients with Hodgkin's lymphoma respond well to pembrolizumab. For example, one study found that 69% of patients had a positive response, with 47% showing partial improvement. Another study found that 78% of patients responded well, and more than half successfully underwent a stem cell transplant afterward.

Regarding safety, the FDA has approved pembrolizumab for treating Hodgkin's lymphoma, indicating it is considered safe for this use. While some side effects can occur, they are usually manageable. Participants should discuss any concerns with their healthcare provider to fully understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Hodgkin's Lymphoma, which typically include chemotherapy and radiation, Pembrolizumab is an immunotherapy that harnesses the body’s own immune system to target cancer cells. Researchers are excited about Pembrolizumab because it specifically blocks the PD-1 pathway, which tumors use to hide from immune cells. This approach not only helps the immune system recognize and attack the cancer but also has the potential to improve outcomes when combined with stem cell transplants. Adding Pembrolizumab before and after the transplant aims to boost long-term remission rates, offering a promising new direction beyond traditional therapies.

What evidence suggests that Pembrolizumab might be an effective treatment for Hodgkin's Lymphoma?

Research has shown that Pembrolizumab yields promising results for treating Hodgkin's Lymphoma. In earlier studies, Pembrolizumab significantly reduced cancer in 67% of patients with recurring or hard-to-treat classic Hodgkin's Lymphoma. Another study found that 69% of patients responded well, with nearly half experiencing partial responses, meaning their tumors shrank but didn't completely disappear. In this trial, participants will receive Pembrolizumab combined with BEAM chemotherapy and autologous stem cell transplant (ASCT), followed by Pembrolizumab maintenance for 1 year. These studies suggest that Pembrolizumab could be an effective option for those fighting Hodgkin's Lymphoma. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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, 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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10602819/

Effectiveness and Safety of Pembrolizumab in Recurrent and ... Although there is currently a high cure rate for cHL, up to 30% of patients in the advanced stages and 5-10% of those in the limited stage ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3046/532366/Efficacy-and-Safety-of-Pembrolizumab-Every-Six

Efficacy and Safety of Pembrolizumab Every Six Weeks in ... We previously reported an objective response rate (ORR) of 67% for patients with R/R cHL, and 50% for patients with R/R PMBCL with 16 months (mo) of follow up.

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda-classical-hodgkin-lymphoma

Pembrolizumab (KEYTRUDA) for classical Hodgkin ... With a median follow-up of 9.4 months (range: 1-15), the overall response rate was 69% (95% CI: 62, 75). This included partial responses in 47% ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6776792/

Pembrolizumab in relapsed or refractory Hodgkin lymphoma With a median follow-up of 10.1 months, pembrolizumab showed excellent antitumor activity, with an overall response rate (ORR) of 69.0% and a complete response ...

5. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100134/538045/Outcomes-of-immune-checkpoint-inhibitor

Outcomes of immune checkpoint inhibitor rechallenge in ... The pooled ORR was 63% (95% CI, 55-70) with a CR rate of 43% (95% CI, 35-52). Median PFS after rechallenge was 13.3 months (95% CI, 7.9-18.8).

6. ashpublications.org ashpublications.org/blood/article/142/10/878/496370/Five-year-follow-up-of-KEYNOTE-087-pembrolizumab

Five-year follow-up of KEYNOTE-087: pembrolizumab ... The median OS was not reached (95% CI, 26.8-NR), and the 5-year OS rate was 53.7% (Figure 3C). Among the 33 patients with disease progression, ...

7. merck.com merck.com/news/data-investigating-keytruda-pembrolizumab-mercks-anti-pd-1-therapy-in-patients-with-classical-hodgkin-lymphoma-presented-at-ash-annual-meeting/

Data Investigating KEYTRUDA® (pembrolizumab), Merck's ... “These early data presented at ASH 2014 are very promising and show response rates of 66 percent with pembrolizumab in patients with classical ...

8. aol.amegroups.org aol.amegroups.org/article/view/6756/html

Effectiveness and safety of pembrolizumab as bridging to ... The response was assessable in 29 patients, 78% of the patients responded to pembrolizumab, 17 (53%) underwent hematopoietic stem cell ...