Pembrolizumab + Chemotherapy for Central Nervous System Lymphoma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Dana-Farber Cancer Institute
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This research study is studying if the investigational drug, Pembrolizumab, in combination with chemotherapy helps primary central nervous system lymphoma with acceptable side effects.
This research study involves a combination of the below drugs:
* Pembrolizumab (a type of monoclonal antibody)
* Methotrexate (a type of anti-metabolite)
* Temozolomide (a type of alkylating agent)
* Rituximab (a type of antibody)
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications that are moderate or strong inhibitors or inducers of certain liver enzymes (CYP3A4/5), or if you are taking enzyme-inducing antiepileptic drugs, you will need to stop them 2 weeks before starting the trial.
What makes the drug combination of Pembrolizumab, Methotrexate, Rituximab, and Temozolomide unique for treating central nervous system lymphoma?
This treatment is unique because it combines Pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs Methotrexate, Rituximab, and Temozolomide, which have shown effectiveness in treating central nervous system lymphoma. This combination aims to enhance the immune response while directly targeting cancer cells, potentially offering a more comprehensive approach than traditional chemotherapy alone.
12356Is the combination of Pembrolizumab, Methotrexate, Rituximab, and Temozolomide safe for treating central nervous system lymphoma?
The combination of methotrexate, rituximab, and temozolomide has been associated with some toxicities, such as effects on the kidneys and bone marrow, but these were considered acceptable in some studies. The safety of these drugs in combination warrants further study, but they have been used with manageable side effects in certain cases.
12456What data supports the effectiveness of the drug combination of Pembrolizumab, Methotrexate, Rituximab, and Temozolomide for central nervous system lymphoma?
Research shows that high-dose methotrexate, temozolomide, and rituximab have been effective in treating primary central nervous system lymphoma, with studies reporting improved survival and responses in patients. Additionally, the combination of rituximab and temozolomide has shown effectiveness in recurrent cases, suggesting potential benefits of these drugs in combination.
12456Eligibility Criteria
This trial is for individuals with newly diagnosed primary central nervous system lymphoma. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and have no conflicting conditions.Inclusion Criteria
My blood, kidney, liver, and clotting tests are all within normal ranges.
My diagnosis is primary CNS lymphoma, confirmed by a biopsy.
My cancer is only in the brain and not anywhere else.
I have not had chemotherapy or radiation for primary central nervous system lymphoma.
I am 18 years old or older.
I have never had an organ transplant or been on ongoing immunosuppressant therapy.
Exclusion Criteria
I have a history of Hepatitis B or an active Hepatitis C infection.
I have an active tuberculosis infection.
My diabetes is not well-managed.
I cannot swallow pills or have major stomach problems.
I have an immune system disorder or am on long-term steroids.
I have had a stem cell transplant from a donor.
I have fluid buildup in my chest, abdomen, or swelling throughout my body.
My cancer is in the eye and hasn't spread to the brain or spinal cord.
I have previously been treated with drugs targeting T-cell receptors.
I have been treated for an autoimmune disease in the last 2 years.
I have another cancer that has gotten worse or needed treatment in the last 3 years.
I have had or currently have lung inflammation treated with steroids.
I am not taking medications that affect cytochrome P450 enzymes.
Participant Groups
The study tests Pembrolizumab combined with chemotherapy (Methotrexate, Temozolomide, Rituximab) to see if it's effective and tolerable for treating central nervous system lymphoma.
2Treatment groups
Experimental Treatment
Group I: Induction Treatment:Experimental Treatment4 Interventions
Participants will be enrolled and will complete procedures as follows, starting at Dose Level 0 for Methotrexate and Temozolomide:
* Baseline visit with assessments and imaging.
* Imaging on cycles 3 and 6 only.
* Cycles 1 through 3:
---Days 3 and 10 of 14 day cycle: Predetermined dose of Rituximab 1x daily.
* Cycles 1, 3, 5, and 7:
---Days 7 through 11 of 14 day cycle: Predetermined dose of Temozolomide 1x daily.
* Cycles 1 through 8:
---Day 1 of 14 day cycle: Predetermined dose of Methotrexate 1x daily.
* Cycles 1, 4, 7
* Day 10 of 14 day cycle: Predetermined dose of Pembrolizumab 1x daily. Treatment will de-escalate per protocol if greater than or equal to 2 out of 6 participants experience a dose-limiting toxicity.
Group II: Consolidation Treatment:Experimental Treatment1 Intervention
4-8 weeks after the completion of Induction Cycle 8, the study doctor will determine if it is appropriate to move on to consolidation therapy and participants will complete:
* Imaging every other cycle.
* Cycles 1 through 15:
* Day 1 of 42 day cycle: Lumbar puncture
* Day 1 of 42 day cycle: Predetermined dose of Pembrolizumab 1x daily.
* End of treatment visit with lumbar puncture and imaging.
* Follow up
Methotrexate is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Trexall for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Mexate for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Methotrexate for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
- Crohn's disease
- Ulcerative colitis
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
Dana Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
Dana-Farber Cancer InstituteLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas. [2018]Methotrexate-based and alkylator-based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma.
Combination therapy with rituximab and temozolomide for recurrent and refractory primary central nervous system lymphoma. [2021]High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population.
Treatment of primary CNS lymphoma. [2021]In this issue of Blood, Omuro et al report the results of a phase 2 study for patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using induction immunochemotherapy (rituximab, high-dose methotrexate [MTX], vincristine, procarbazine) followed by a novel consolidation high-dose chemotherapy (thiotepa, busulfan, cyclophosphamide) and autologous stem cell transplantation (HDC-ASCT).
Methotrexate-cytarabine-dexamethasone combination chemotherapy with or without rituximab in patients with primary central nervous system lymphoma. [2018]High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen).
[Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma]. [2021]To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL).
Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C. [2023]The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.