Pembrolizumab + Bendamustine for Hodgkin's Lymphoma

Recruiting in Toronto (>99 mi)

Overseen By John Kuruvilla, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Investigational agents, Monoclonal antibodies

Disqualifiers: Active malignancy, Autoimmune 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

Compensation: Varies

Number of Visits: 35

Duration: 24 months

37 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot be on any other chemotherapy, radiotherapy, or investigational agents within 4 weeks of starting the trial treatment.

What data supports the effectiveness of the drug combination Pembrolizumab and Bendamustine for treating Hodgkin's Lymphoma?

Research shows that Bendamustine, when used with other drugs, has high response rates in treating relapsed or refractory Hodgkin's Lymphoma, with 85% of patients responding to treatment. This suggests that Bendamustine can be effective in similar settings, potentially supporting its use with Pembrolizumab. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Bendamustine generally safe for humans?

Bendamustine has been used safely in treating certain types of blood cancers, but it can cause skin reactions, including severe rashes, especially when combined with other drugs. Pembrolizumab is generally considered safe, but like all medications, it can have side effects, so it's important to discuss potential risks with your doctor. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a phase 2 open-label study to test the safety and effectiveness of combining pembrolizumab and bendamustine in patients with relapsed (cancer that has come back or started getting worse) or refractory (cancer that is not responding or has stopped responding to treatment) Hodgkin lymphoma.

Research Team

John Kuruvilla, MD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for adults with relapsed or refractory classical Hodgkin Lymphoma who've had standard chemotherapy and possibly a stem cell transplant. They should be in good physical condition (ECOG 0-1), have a life expectancy over 90 days, and adequate organ function. Women must test negative for pregnancy and all participants agree to use contraception during the study.

Inclusion Criteria

I have been treated with pembrolizumab or similar, but not with bendamustine.

I had a stem cell transplant over 100 days ago, with mild or no side effects, and I'm not on immunosuppressants.

I am a woman who can have children and have a recent negative pregnancy test.

Exclusion Criteria

I am eligible for a stem cell transplant but may choose not to have it.

I have an autoimmune disease that needed treatment in the last 2 years.

I have had a stem cell transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and bendamustine in 3-week cycles

24 months

Up to 35 cycles, with pembrolizumab every cycle and bendamustine on Days 1 and 2 of the first 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Bendamustine Hydrochloride
• Pembrolizumab

Trial Overview The study tests combining pembrolizumab, an immunotherapy drug, with bendamustine hydrochloride, a chemotherapy agent. It's open-label meaning everyone knows what treatment they're getting. The goal is to see if this combo is safe and works better for those whose lymphoma has returned or isn't responding.

Participant Groups

Group I: Pembrolizumab and Bendamustine Experimental Treatment 2 Interventions

The study drugs will be given in 3 week periods called cycles. Pembrolizumab is available in powder form or as a liquid for infusion. Pembrolizumab at a dose of 200 mg will be given over 30 minutes, once every cycle for up to 35 cycles (approximately 24 months). Bendamustine is available in powder form for injection. Bendamustine at a dose of 90 mg/m2 will be given over 60 minutes, on Days 1 and 2 of every cycle for up to 6 cycles.

Bendamustine Hydrochloride is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Approved in European Union as Levact for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)
• Multiple myeloma

Approved in Japan as Ribomustin for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study of 67 adults with relapsed indolent B-cell or mantle cell lymphoma, the combination of bendamustine and rituximab achieved a high overall response rate of 92%, with a median duration of response of 21 months.

The treatment was generally well tolerated, although myelosuppression was the primary side effect, affecting 36% of patients with grade 3 or 4 neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. Robinson, KS., Williams, ME., van der Jagt, RH., et al.[2022]

Bendamustine is effective in treating low-grade B-cell lymphoma, particularly follicular lymphoma, as shown in a study of 127 patients who received at least three courses of the drug.

The lymphocyte-monocyte ratio (LMR) is a significant predictor of treatment efficacy, with an LMR ≤2.0 indicating earlier disease progression and shorter time to next treatment, suggesting that monitoring LMR could enhance treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte-monocyte ratio (LMR) can predict bendamustine therapeutic efficacy in low-grade B-cell lymphoma. Shimono, J., Izumiyama, K., Ito, S., et al.[2021]

Bendamustine demonstrated a 50% overall response rate in patients with refractory or relapsed T-cell lymphomas, with 28% achieving a complete response and 22% a partial response, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with manageable side effects, the most common being neutropenia (30%) and thrombocytopenia (24%), suggesting that bendamustine has an acceptable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. Damaj, G., Gressin, R., Bouabdallah, K., et al.[2022]

The T(R)EC regimen, which replaces ifosfamide with bendamustine, demonstrated high response rates of 85% in classic Hodgkin lymphoma and 65% in diffuse large B cell lymphoma, indicating its efficacy as a treatment for relapsed or refractory cases.

This outpatient treatment was found to be safe, with no dose-limiting toxicities and successful stem cell collection in 30 out of 32 patients, making it a promising alternative to the traditional (R)ICE regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. Budde, LE., Wu, D., Martin, DB., et al.[2022]

The combination therapy of bendamustine, mitoxantrone, and rituximab (BMR) showed a high overall response rate of 89% in patients with relapsed or refractory indolent lymphomas, including a complete response in 35% of patients after four treatment cycles.

BMR demonstrated a favorable safety profile with manageable toxicities, primarily reversible myelosuppression, and only 4% of patients required unexpected hospitalizations, indicating it is a promising outpatient treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Weide, R., Hess, G., Köppler, H., et al.[2019]

Bendamustine hydrochloride has been associated with serious adverse events such as Stevens-Johnson syndrome and toxic epidermal necrolysis, leading to important label updates regarding its safety and administration.

Despite these risks, the long-term pharmacovigilance data suggest that bendamustine maintains a favorable risk-benefit profile, making it a valuable treatment option for patients with chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety experience with bendamustine for injection in a real-world setting. Martin, P., Barr, PM., James, L., et al.[2017]

Bendamustine demonstrated a high objective response rate of 74.3% in 99 patients with relapsed/refractory Hodgkin and non-Hodgkin lymphoma, indicating its efficacy as a salvage treatment after multiple lines of chemotherapy.

The most common side effects included lymphopenia, anemia, and neutropenia, with serious side effects occurring in a minority of patients, suggesting that while bendamustine is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. Karadurmus, N., Paydas, S., Esin, E., et al.[2022]

Bendamustine, an FDA-approved anti-cancer drug for chronic lymphocytic leukemia and non-Hodgkin lymphoma, can cause severe skin reactions when used with certain other medications, such as allopurinol and rituximab.

A case study highlighted a patient with non-Hodgkin lymphoma who experienced a severe cutaneous reaction to bendamustine, emphasizing the need for awareness of this potential adverse effect in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe cutaneous interface drug eruption associated with bendamustine. Alamdari, HS., Pinter-Brown, L., Cassarino, DS., et al.[2015]

The BeGEV±X regimen, which combines bendamustine with other agents, showed promising efficacy in treating relapsed/refractory non-Hodgkin lymphoma, achieving a complete response rate of 33% and an overall response rate of 50% among 18 patients studied.

While the treatment was effective, it was associated with significant adverse effects, particularly hematologic toxicities and infections, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy Analysis of Bendamustine-Based Combination Regimen in Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma]. Guo, YT., Li, F., Dong, WM., et al.[2022]

Bendamustine is a unique cancer treatment that combines alkylating and antimetabolite properties, making it effective against certain blood cancers like chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

It has been approved by the US FDA for patients whose cancer has not responded to or has progressed after rituximab treatment, and it can be used alone or in combination with other therapies, showing promising efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ujjani, C., Cheson, BD.[2015]

References

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

Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Lymphocyte-monocyte ratio (LMR) can predict bendamustine therapeutic efficacy in low-grade B-cell lymphoma. [2021]

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

Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. [2022]

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

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. [2022]

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

High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). [2019]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety experience with bendamustine for injection in a real-world setting. [2017]

7. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]

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

Severe cutaneous interface drug eruption associated with bendamustine. [2015]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy Analysis of Bendamustine-Based Combination Regimen in Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma]. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. [2015]