Pembrolizumab + Gemcitabine for Cutaneous T-Cell Lymphoma

Recruiting at 14 trial locations

Overseen By Steven Horwitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Pregnancy, Active infection, 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: Unknown

Duration: 6 months

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of pembrolizumab (an immunotherapy drug) and gemcitabine (a chemotherapy drug) to determine its effectiveness for specific skin-related lymphomas, namely mycosis fungoides and Sézary syndrome. Researchers aim to discover if these drugs work well together to improve symptoms or slow the disease. It targets individuals diagnosed with these conditions who have tried at least one treatment and have visible skin symptoms covering 10% or more of their body. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from potentially effective therapies.

Will I have to stop taking my current medications?

The trial requires that any previous systemic anti-cancer therapy be stopped at least 2 weeks before starting the study treatment. However, if you are on a stable dose of topical or systemic steroids (up to 10 mg/day of prednisone), you may continue if stopping them could cause a flare-up or other issues.

Is there any evidence suggesting that the combination of pembrolizumab and gemcitabine is likely to be safe for humans?

Research has shown that pembrolizumab, when combined with gemcitabine, may effectively treat mycosis fungoides and Sézary syndrome, both types of skin cancer. Pembrolizumab is a medication that aids the immune system in fighting cancer cells.

Earlier studies have found pembrolizumab alone to be generally well-tolerated, with common side effects like tiredness and mild skin reactions. Gemcitabine, a chemotherapy drug, has known side effects such as nausea and reduced white blood cell counts, which are usually manageable.

When used together, pembrolizumab and gemcitabine have not caused any unexpected severe side effects in early trials. These trials are in the middle stages, indicating some evidence of safety, though more information is still being collected. Prospective trial participants should consult their doctor about possible side effects and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Gemcitabine for treating cutaneous T-cell lymphoma because of its unique approach. Pembrolizumab, an immunotherapy drug, works by unleashing the immune system to target and destroy cancer cells, offering a novel mechanism compared to the traditional chemotherapy options like methotrexate or bexarotene. Gemcitabine, on the other hand, is a well-established chemotherapy agent that disrupts cancer cell DNA. The combination of these two treatments could potentially enhance the effectiveness and broaden the therapeutic impact, providing new hope for patients with advanced stages of mycosis fungoides or Sezary syndrome.

What evidence suggests that the combination of pembrolizumab and gemcitabine might be an effective treatment for mycosis fungoides and Sézary syndrome?

Research has shown that combining pembrolizumab with gemcitabine might be promising for treating mycosis fungoides and Sézary syndrome. In this trial, participants will receive both pembrolizumab, which helps the immune system find and attack cancer cells, and gemcitabine, which directly kills these cells. Studies on similar conditions have demonstrated that pembrolizumab alone can shrink tumors. The aim is for the combined treatments to be more effective than either one alone. Early results are encouraging, but further research is needed to confirm its effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with mycosis fungoides or Sézary syndrome, who have tried at least one systemic therapy before, can join this trial. They should be relatively healthy (ECOG score 0-1) and not have had certain treatments recently. People with organ transplants, other active cancers, severe infections, or immune conditions that need treatment are excluded.

Inclusion Criteria

I have been treated with gemcitabine before.

Participant provides written informed consent

I have received at least one treatment for my cutaneous T-cell lymphoma.

Exclusion Criteria

I have been diagnosed with active lymphoma in my brain or spinal cord.

I have an active case of tuberculosis.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and gemcitabine to assess efficacy in treating mycosis fungoides and Sézary syndrome

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Pembrolizumab

Trial Overview The trial is testing if pembrolizumab combined with gemcitabine works for advanced mycosis fungoides and Sézary syndrome. Participants will receive both drugs to see how effective they are together in treating these conditions.

How Is the Trial Designed?

Group I: Participants with confirmed mycosis fungoides/Sezary syndrome Experimental Treatment 2 Interventions

Participants will have confirmed mycosis fungoides/Sezary syndrome, disease stage IB (defined as patches, plaque, or papules that involve 10% of the skin surface viscera) or higher.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

A retrospective study of 64 patients with advanced-stage cutaneous T-cell lymphoma (CTCL) and blastic plasmacytoid dendritic cell neoplasia (BPDCN) showed that low-dose gemcitabine (1,800 mg/m2) achieved an overall response rate of 62% and a median progression-free survival of 12 months, comparable to standard dosing.

The low-dose regimen significantly improved safety, with only 3 out of 63 patients experiencing serious adverse events, while 73% reported only minor to moderate side effects, indicating better tolerability compared to the standard higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Advanced-Stage Cutaneous Lymphoma under Low-Dose Gemcitabine Treatment: Real-Life Data from the German Cutaneous Lymphoma Network. Blazejak, C., Stranzenbach, R., Gosman, J., et al.[2022]

Gemcitabine, a purine analogue, has been identified as a practical and effective treatment option for mycosis fungoides that has transformed into large cerebriform cells, which typically resist other treatments.

The review includes three illustrative cases demonstrating that gemcitabine monotherapy is not only safe but also shows efficacy in managing this more aggressive form of cutaneous T cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of transformed mycosis fungoides with intermittent low-dose gemcitabine. Awar, O., Duvic, M.[2022]

In a study of 118 patients with cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS), the overall survival for MF patients was 17.7 years, while SS patients had a median survival of 3.5 years, indicating significant differences in outcomes based on the type of CTCL.

The most common treatments for MF included low-dose methotrexate and interferon-alpha, while SS patients often received bexarotene and extracorporeal photopheresis, highlighting the need for more innovative therapies to be integrated into earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience. Polgárová, K., Polívka, J., Kodet, O., et al.[2022]

In a multicenter study of 23 patients with advanced-stage cutaneous T-cell lymphomas (CTCL), gemcitabine demonstrated early efficacy, with 62.5% of patients responding after three cycles of treatment.

Despite its effectiveness, the study revealed a high incidence of serious adverse events, including severe neutropenia in 30% of patients and other significant complications, challenging the previously reported safety profile of gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine treatment in cutaneous T-cell lymphoma: a multicentre study of 23 cases. Jidar, K., Ingen-Housz-Oro, S., Beylot-Barry, M., et al.[2022]

In a retrospective study of 25 patients with advanced cutaneous T cell lymphoma (CTCL) who had previously undergone 1 to 8 therapies, gemcitabine treatment resulted in a 48% overall response rate and a 20% complete response rate, indicating its efficacy as a second-line treatment.

The long-term outcomes showed a 15-year overall survival rate of 47%, with no severe hematological adverse events reported, confirming gemcitabine's safety and effectiveness as a single-agent therapy for pretreated CTCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of patients with advanced-stage cutaneous T cell lymphoma treated with gemcitabine. Pellegrini, C., Stefoni, V., Casadei, B., et al.[2022]

In a phase II study involving patients with cutaneous T-cell lymphoma who had previously failed standard treatments, the combination of gemcitabine and bexarotene showed that 80% of patients had a reduction in disease severity, but only 31% achieved a partial response after 12 weeks.

The median progression-free survival was 5.3 months and median overall survival was 21.2 months, indicating that while the combination treatment was feasible, its efficacy was lower than expected compared to gemcitabine used alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma. Illidge, T., Chan, C., Counsell, N., et al.[2022]

Gemcitabine, administered weekly at doses of 1,000-1,200 mg/m2, showed significant improvement in skin lesions for two patients with advanced-stage mycosis fungoides who did not respond to prior CHOP therapy.

The treatment was well tolerated, with no severe hematological or hepatic side effects reported, indicating that gemcitabine is a safe and effective monotherapy for cutaneous T-cell lymphoma (CTCL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gemcitabine Monotherapy for Advanced Mycosis Fungoides--Two Case Reports and a Literature Review]. Masuzawa, M., Takasu, H., Amoh, Y.[2022]

In a Phase II trial involving 32 untreated patients with advanced cutaneous T-cell lymphoma (CTCL), gemcitabine demonstrated significant efficacy, with 22% achieving a complete response and 53% achieving a partial response.

The treatment was well tolerated, showing only mild hematologic toxicity and no severe side effects, indicating that gemcitabine could be a safe option for patients with untreated CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Marchi, E., Alinari, L., Tani, M., et al.[2022]

In a small case series of four patients with advanced cutaneous T-cell lymphoma (CTCL), a combination of gemcitabine and vinorelbine resulted in partial remission for all patients, although the remission lasted only 2 to 6 months.

The treatment was associated with some side effects, including neutropenia in two patients and acute hepatitis in one, which led to the discontinuation of therapy, highlighting the need to balance efficacy with safety in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and vinorelbine treatment in cutaneous T-cell lymphoma in four patients. Affandi, AM., Blumetti, TP., Wells, J., et al.[2022]

In a phase II trial involving 44 patients with relapsed or refractory cutaneous T-cell lymphomas, gemcitabine demonstrated efficacy, with 11.5% achieving complete responses and 59% achieving partial responses, indicating its potential as a treatment option.

Gemcitabine was well tolerated, showing only mild hematologic toxicity and no significant nausea, vomiting, or organ toxicity, suggesting a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. Zinzani, PL., Baliva, G., Magagnoli, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04960618

Study Details | NCT04960618 | Pembrolizumab in ... The purpose of this study is to find out whether the combination of pembrolizumab and gemcitabine is an effective treatment for mycosis fungoides and Sézary ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-11629

Pembrolizumab in Combination with Gemcitabine ... This phase II trial tests whether pembrolizumab in combination with gemcitabine work to shrink tumors in patients with mycosis fungoides and Sezary syndrome.

3. withpower.com withpower.com/trial/phase-3-syndrome-8-2021-21832

Pembrolizumab + Gemcitabine for Cutaneous T-Cell ... Pembrolizumab helps the immune system attack cancer, while gemcitabine kills cancer cells directly. The goal is to see if this combination is more effective ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6943974/

Pembrolizumab in Relapsed and Refractory Mycosis ... To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).

5. clfoundation.org clfoundation.org/pembrolizumab-combination-gemcitabine-people-advanced-mf-or-ss

Pembrolizumab in Combination With Gemcitabine ... Brief Summary: The purpose of this study is to find out whether the combination of pembrolizumab and gemcitabine is an effective treatment for mycosis fungoides ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10585160/

Advances in the treatment of mycoses fungoides and ... Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8415544/

Immune Check Point Inhibitors in Primary Cutaneous T- ... Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells.