Taking part in a clinical trial may be the best therapy for some non-Hodgkin lymphoma (NHL) patients. Clinical trials are under way to develop treatments that increase the remission rate of or cure the disease. Clinical trials are carefully designed and reviewed by expert clinicians and researchers to ensure safety and scientific accuracy. The Leukemia & Lymphoma Society continues to invest funds in NHL research.
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Current NHL Research and Clinical Trials
Below are some of the types of NHL research and clinical trials under way:
- Brentuximab vedotin (Adcetris®) targets cluster designation (CD) 30 (CD30) and is used for treating peripheral T-cell lymphomas and Hodgkin lymphomas. It is under study in clinical trials for treating other previously treated NHLs.
- Yttrium-90+ibritumomab tiuxetan (Zevalin®) is approved by the Food and Drug Administration (FDA) for previously untreated follicular NHL patients who achieve a partial or complete response to first-line chemotherapy and for relapsed/refractory follicular patients. The effectiveness of this agent is now being studied in the retreatment of lymphoma, as therapy for newly diagnosed indolent lymphoma, as therapy for aggressive forms of NHL in combination, either with or following other drug regimens, and as part of high-dose therapy programs along with autologous stem cell transplantation.
- Ofatumumab (Arzerra®) is an anti-CD20 antibody that is approved by the FDA for treatment of relapsed chronic lymphocytic leukemia (CLL). It is now being studied in clinical trials in various combinations for the treatment of mantle cell, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma.
- Obinutuzumab (Gazyva®) is an antibody that targets CD20. It is being used in the treatment of some types of NHLs including refractory follicular lymphoma. It is being studied in clinical trials (in combination with other agents) for treating relapsed and refractory CLL and small-cell lymphocytic leukemia (SLL).
- Blinatumomab (Blincyto®), a bispecific antibody that targets CD19 and CD3, is under investigation for heavily pretreated patients DLBCL and indolent lymphoma.
- Mogalizumab (Poteligeo) is a monoclonal antibody that targets chemokine receptor 4 (CCR4). It is in clinical trials for the treatment of patients with cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.
- Idelalisib (Zydelig®), is a PI3K inhibitor which is approved by the FDA for the treatment of chronic lymphocytic leukemia and for the treatment of refractory indolent NHL. This agent is being explored in combination with chemotherapy, monoclonal antibodies and other new drugs for the treatment of heavily pretreated for relapsed or refractory indolent B-cell NHL, mantle cell lymphoma (MCL) and marginal zone lymphoma patients.
- The oral selective inhibitor of nuclear export (SINE) selinexor (KPT-330) is being studied for the treatment of DLBCL. This drug acts by blocking the transport of nuclear proteins in malignant cells, leading to cell death.
- Antifolate pralatrexate (Foloytn®), approved for various T-cell lymphoma subtypes, is being studied as a single agent and in combination with other chemotherapy drugs for treating various relapsed and refractory B-cell and T-cell NHLs. Pralatrexate is an antifolate drug that disrupts processes in cells that are required for cell replication.
- mTOR inhibitors work to slow or inhibit the progression of MCL by reducing cell expression of cyclin D1 and other important proteins responsible for cancer cell growth. Blocking mTOR activity in MCL leads to antiproliferative effects and, sometimes, to cell death. They have demonstrated activity in MCL alone and in combination with other therapies. Examples of mTOR inhibitors is under investigation include
- Temsirolimus (Torisel®) for treatment of relapsed MCL. Several studies are evaluating temsirolimus as combination therapy with conventional chemotherapy (single agent or combination), immunomodulatory agents (eg, lenalidomide), monoclonal antibodies (eg, rituximab), alkylating agents (eg, bendamustine) and proteasome inhibitors (eg, bortezomib) for untreated and for relapsed/refractory MCL.
- Everolimus (Afinitor®) is a medication that blocks cancer proliferation by cutting off the blood supply to cancer cells. This agent is being studied in patients with advanced, refractory, or relapsed MCL. This drug is also being studied in combination with other drugs, such as lenalidomide, bortezomib and bendamustine/rituximab, for relapsed MCL.
- Cell cycle inhibitors interfere with the process of cell division that enables tumors to grow.
- Palbociclib (Ibrance®) is a cyclin D-dependent kinase 4/6 (CDK4/6) inhibitor that decreases tumor cell proliferation and sensitizes ibrutinibresistant MCL cells to PI3K inhibitors. It is being studied in clinical trials as a single agent and in combination with other drugs such as bortezomib and ibrutinib for relapsed and refractory MCL patients. It is also being studied in combination with other drugs to treat various indolent and aggressive NHLs.
- Abemaciclib (Verzenio®), a CDK 4/6 inhibitor, has also shown clinical activity in heavily pretreated MCL and is being studied in clinical trials.
- Flavopiridol (Alvocidib®) is a pan-CDK inhibitor being studied in combination with fludarabine and rituximab for both newly diagnosed and previously treated MCL. Another study, currently in trials, combines flavopiridol and bortezomib for the treatment of relapsed MCL and the combination is being found to be safe and well tolerated.
- Lenalidomide (Revlimid®) is an immunomodulator, which regulates the function of the immune system and has the capability of slowing the rate at which cancer cells grow and multiply, is FDA approved for the treatment of patients who have relapsed or refractory MCL. This drug may be given if firsttime treatment does not work. It is being studied as monotherapy and in combination with rituximab and/or other agents in patients who have relapsed or refractory DLBCL, MCL, follicular lymphoma and CLL.
- Proteasome inhibitors affect cell pathways by blocking the activity of enzymes that are needed for cell proliferation and survival.
- Bortezomib (Velcade®), which may also stop the growth of cancer cells by blocking blood flow to the tumor, is being studied together with rituximab and some chemotherapy combinations in both untreated and refractory MCL and for other aggressive NHLs.
- Carfilzomib (Kyprolis®), which is FDA approved for the treatment of patients with multiple myeloma, is in clinical studies as single-agent therapy and as combination therapy for patients with relapsed/refractory MCL. Carfilzomib works by preventing cancer cells from repairing themselves, which may cause cell death.
- Vorinostat (Zolinza®) is a histone deacetylase (HDAC) inhibitor which are a class of drugs that address “epigenetic” changes in the DNA and cause a chemical reaction in tumor cells, preventing them from dividing. It has shown promising results in newly diagnosed MCL, especially when it is used in combination with other agents, such as rituximab and cladribine.
- Reduced-Intensity Stem Cell Transplantation (Nonmyeloablative Allogeneic Transplantation) may be a an option for older and sicker patients. Clinical trials are under way to evaluate this type of transplantation and determine its effectiveness as treatment for many blood cancers, including some NHL subtypes. As a result, stem cell transplantation may be a possible treatment for patients aged 60 to 70 years and older. Patients undergo conditioning for a reduced-intensity transplant; they receive lower doses of chemotherapy drugs and/or radiation in preparation for the transplant. Immunosuppressive drugs are used to prevent rejection of the graft (the donor immune cells), thereby allowing the engrafted immune cells to attack the recipient’s disease. The effectiveness of reduced-intensity transplantation is due to the graft-versus-lymphoma effect of the donor’s lymphocytes rather than to high doses of chemotherapy.
- Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that consists of engineering a patient’s own immune cells to recognize and then attack cancerous tumors. This approach has shown very promising results in patients with blood cancers. The patient’s T cells are genetically engineered to produce CARs on their surface. These receptors recognize and bind to a specific target found on the cancer cells. Axicabtagene ciloleucel (Yescarta™) and tisagenlecleucel (Kymriah™) are currently approved for lymphoma.
For more information on this type of therapy, please see the LLS booklet Chimeric Antigen Receptor (CAR) T-Cell Therapy Facts.
- Nivolumab (Opdivo®) is a programmed cell death 1 (PD-1) checkpoint inhibitor that has shown positive results in other cancers, such as melanoma. Nivolumab is being studied both as a single agent and in combination with other drugs for the treatment of B-cell and T-cell NHLs.
- Pidilizumab is a PD-1 checkpoint inhibitor. It is being studied in clinical trials for the treatment of relapsed follicular lymphoma